Halogenating agents

ABSTRACT

Disclosed are a fluorinating agent represented by the general formula (1):  
                 
 
     wherein R 1  to R 4  are a substituted or unsubstituted, saturated or unsaturated alkyl group or a substituted or unsubstituted aryl group, and can be the same or different; R 1  and R 2  or R 3  and R 4  can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms; or R 1  and R 3  can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms, for example:  
                 
 
     a preparation process of the fluorinating agent and a process for preparing fluorine compounds by reacting various compounds with the fluorinating agent. The invention has also disclosed that the fluorinating agent is very effective for fluorinating oxygen containing functional compounds.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The present invention relates to a novel halogenating agent,preparation process and use of the agent.

[0003] 2. Related Art of the Invention

[0004] Many processes have been conventionally known related to thehalogenating reaction of organic compounds. Halogenating agents whichcan be generally used are hydrogen halogenide, halogen-phosphoruscompounds, halogen-sulfur compounds and halogen simple substances.However, these substances have high corrosivity and toxicity, and manyof them require specific equipment and technique for handling theseagents. Consequently, in view of ease handling, safety and reactivity,development research on various halogenating agents has been continuedstill now. Particularly in the preparation of fluorine compounds,fluorinating agents are generally very dangerous. Thus, specificequipment and techniques having a further high level as compared withother halogenating reaction are required and also lead to higher load ineconomy.

[0005] Fluorinating agents which have been conventionally used for afluorinating reaction are fluorine, hydrogen fluoride, andtetrafluorinated sulfur. However, these conventional fluorinating agentsare difficult to handle due to toxicity, corrosivity and danger ofexplosion in the reaction step and require specific equipment andtechniques. Further, poor selectivity of a fluorine bonding in thereaction is also a problem. On the other hand, development of newproducts utilizing fluorine compounds has been carried out in functionalmaterials, physiologically active substances and other various fields.In recent years, various fluorinating agents have been developed to copewith these demands.

[0006] For example, as a representative agent which has been developedfor a fluorinating agent of a hydroxyl group, carboxyl group and otheroxygen containing functional groups, U.S. PATENT NO. 3,976,691 hasdisclosed DAST (diethylaminosulfurtrifluoride). DAST has been introducedas an excellent fluorinating agent of oxygen in an alcoholic hydroxylgroup or a carbonyl group. However, in the preparation of DAST, highlydangerous tetrafluorinated sulfur is reacted withdimethylaminotrimethylsilane at a low temperature of −78° C. to −60° C.Thus, a specific manufacturing facility is required. As to safety,explosion has been reported on the production and use of DAST [J.Fluorine Chem., 42 137 (1989)].

[0007] Further, WO 96/04297 has described thattetraalkyl-fluoroform-amidinium=salt is an excellent fluorinating agentof a carboxyl group. However, no description has been found on thefluorinating reaction of other functional groups. The application hasdescribed that halogen ions are included as a counter ion oftetraalkyl-fluoroformamidinium salt. However, in practice, PF₆ is anonly one example shown as a counter ion. Therefore, the presentinventors have prepared1,3-dimethyl-2-fluoroimidazolinium=hexafluorophosphate in accordancewith the process of WO 96/04297, and used for the replacement ofindividual hydroxyl group on benzoic acid, benzyl alcohol and n-octanolinto fluorine. As a result, benzoyl fluoride has been formed frombenzoic acid. However, formation of fluorine compounds could not beobserved in the fluorinating reaction of benzyl alcohol and n-octanol.Japanese Laid-Open Patent HEI 4-308538 has disclosed a halogenatingreaction of primary alcohol by using a haloiminium salt as ahalogenating agent. Japanese Laid-Open Patent HEI 9-67299 has describeda halogenation reaction of carboxylic acid. Both literatures havedescribed that the counter ion of haloiminium salt includes a halogenion. However, in practice, the counter ion is an example of Cl^(—)alone. Quite no description is found on a fluorinating agent inparticular.

[0008] Further, DE 2627986 and Japanese Laid-Open Patent SHO 52-156810have described use of bis-dialkylaminodifluoromethane as a reactioncatalyst in the preparation of perfluoroalkoxypropionyl fluoride.However, no description has been found on a fluorinating agent. Thepreparation is carried out by reacting hexafluoropropene oxide withtetraalkylurea, and the source of fluorine is expensive and difficult tohandle.

[0009] As a mentioned above, the fluorinating agent of an oxygencontaining functional group has not yet satisfactorily developed for usein industry in view of preparation process, selectivity, yield andeconomy.

SUMMARY OF THE INVENTION

[0010] One object of the invention is to provide a halogenating agent ofan organic compound, a fluorinating agent in particular, whicheliminates the above problems of the prior art and can be prepared by atechnically and economically improved process in industry and isexcellent in reactivity and economy, to provide a preparation process ofthe halogenating agent, and to provide a preparation process ofcompounds obtained by halogenating, fluorinating in particular, variousorganic compounds with the agent.

[0011] As a result of an intensive investigation in order to solve theabove objects, the present inventors have found that the compoundrepresented by the formula (1):

[0012] wherein R¹ to R⁴ is a substituted or unsubstituted, saturated orunsaturated alkyl group or a substituted or unsubstituted aryl group andcan be the same or different; R¹ and R² or R³ and R⁴ can bond to form aring including a nitrogen atom or a nitrogen atom and other heteroatoms; or R¹ and R³ can bond to form a ring including a nitrogen atom ora nitrogen atom and other hetero atoms, is a novel excellentfluorinating agent which is selective for a hydroxyl group, carboxylgroup, formyl group, ketone group and other oxygen containing functionalgroups, and further found that application to the fluorinating reactionrequires no specific equipment and technique and can be carried out inextreme safety and with ease.

[0013] Further, they have found that the compound represented by theformula (1) can be obtained by way of a halogen exchange reaction of thecompound represented by the formula (14):

[0014] wherein X₂ and X₃ are chlorine or bromine atoms and can be thesame or different; R¹ to R⁴ is a substituted or unsubstituted, saturatedor unsaturated alkyl group or a substituted or unsubstituted aryl groupand can be the same or different ; R¹ and R² or R³ and R⁴ can bond toform a ring including a nitrogen atom or a nitrogen atom and otherhetero atoms; or R¹and R³ can bond to form a ring including a nitrogenatom or a nitrogen atom and other hetero atoms, and thus no specificequipment and technique are required and can be safely manufactured inindustry

[0015] They have also found that the fluorinating agent represented bythe formula (1) can be recovered after fluorinating reaction in the formof urea and can be reused in economy for the raw material of thecompound represented by the formula (14).

[0016] Further, they have also found that the compound represented bythe formula (15):

[0017] wherein X₄ and X₅ are halogen atoms and can be the same ordifferent except that both of X₄ and X₅ are fluorine atoms, chlorineatoms or bromine atoms; R¹ to R⁴ is a substituted or unsubstituted,saturated or unsaturated alkyl group or a substituted or unsubstitutedaryl group and can be the same or different; R¹and R² or R³ and R⁴ canbond to form a ring including a nitrogen atom or a nitrogen atom andother hetero atoms, is an excellent, novel halogenating agent which isselective for a hydroxyl group, carboxyl group, formyl group and otheroxygen containing functional groups, and further found that applicationto the halogenation reaction requires no specific equipment andtechnique and can be carried out in extreme safety with ease.

[0018] That is, the aspect of the invention will be illustrated from (1)to (45) below.

[0019] (1) A fluorinating agent represented by the formula (1):

[0020] wherein R¹ to R⁴ is a substituted or unsubstituted, saturated orunsaturated alkyl group, saturated or unsaturated aryl group, and can bethe same or different; R¹and R² or R³ and R⁴ can bond to form a ringincluding a nitrogen atom or a nitrogen atom and other hetero atoms; orR¹ and R³ can bond to form a ring including a nitrogen atom or anitrogen atom and other hetero atoms.

[0021] (2) A fluorinating agent according to the above (1) wherein thefluorinating agent represented by the formula (1) is represented by theformula (2):

[0022] wherein a is an integer of 2 or 3, R⁵ and R⁶ are substituted orunsubstituted, saturated or unsaturated lower alkyl groups having 1 to 6carbon atoms and can be the same or different.

[0023] (3) A fluorinating agent according to the above (2) wherein thefluorinating agent represented by the formula (2) is2,2-difluoro-1,3-dimethylimidazolidine represented by the formula (3):

[0024] (4) A fluorinating agent according to the above (2) wherein thefluorinating agent represented by the formula (2) is2,2-difluoro-1,3-di-n-butylimidazolidine represented by the formula (4):

[0025] (5) A fluorinating agent according to the above (1) wherein thefluorinating agent represented by the formula (1) is represented by theformula(5):

[0026] wherein R⁷ to R¹⁰ is a substituted or unsubstituted, saturated orunsaturated lower alkyl group having 1 to 6 carbon atoms, and can be thesame or different; R⁷ and R⁸ or R⁹ and R¹⁰ can bond to form a ringincluding a nitrogen atom or a nitrogen atom and other hetero atoms; orR⁷ and R⁹ can bond to form a ring including a nitrogen atom or anitrogen atom and other hetero atoms.

[0027] (6) A fluorinating agent according to the above (5) wherein thefluorinating agent represented by the formula (5) isbis-dimethylamino-difluoromethane represented by the formula (6):

[0028] (7) A fluorinating agent according to the above (5) wherein thefluorinating agent represented by the formula (5) isbis-di-n-butylamino-difluoromethane represented by the formula (7):

[0029] (8) A preparation process of a fluorine compound represented bythe formula (8-1):

R¹¹—F  (8-1)

[0030] wherein R¹¹ is a substituted or unsubstituted alkyl group and caninclude an unsaturated group therein, comprising reacting a compoundhaving an alcoholic hydroxyl group and represented by the formula (8):

R¹¹—OH  (8)

[0031] wherein R¹¹ is the same as in the formula (8-1), with the abovefluorinating agent represented by the formula (1).

[0032] (9) A preparation process of a fluorine compound represented bythe formula (9-1):

[0033] wherein Y¹ is an electrophilic substituent, b is an integer of 1to 5, c is an integer of 1 to 5, and b+c≦6, comprising reacting acompound of phenol species or thiophenol species represented by theformula (9):

[0034] wherein Q is an oxygen or a sulfur atom, and Y¹, b and c are thesame as in the formula (9-1), with the above fluorinating agentrepresented by the formula (1).

[0035] (10) A preparation process of a fluorine compound represented bythe formula (10-1):

R¹²—CHF₂  (10-1)

[0036] wherein R¹² is a substituted or unsubstituted, saturated orunsaturated alkyl group, or a substituted or unsubstituted aryl group,comprising reacting an aldehyde compound represented by the formula(10):

R¹²—CHO  (10)

[0037] wherein R¹² is the same as in the formula (10-1), with the abovefluorinating agent represented by the formula (1).

[0038] (11) A preparation process of a fluorine compound represented bythe formula (11-1):

[0039] wherein R¹³ and R¹⁴ are a substituted or unsubstituted alkylgroup or a substituted or unsubstituted aryl group and can be the sameor different; the alkyl group can include unsaturated group, and R¹³ andR¹⁴ can bond to form a ring, comprising reacting a ketone compoundrepresented by the formula (11):

[0040] wherein R¹³ and R¹⁴ are the same as in the formula (11-1), withthe above fluorinating agent represented by the formula (1).

[0041] (12) A preparation process of an acid fluoride represented by theformula (12-1):

R¹²—COF  (12-1)

[0042] wherein R¹⁵ is a substituted or unsubstituted, saturated orunsaturated alkyl group or a substituted or unsubstituted aryl group,comprising reacting a carboxyl compound represented by the formula (12):

R¹⁵—COOH  (12)

[0043] wherein R¹⁵ is the same as in the formula (12-1), with the abovefluorinating agent represented by the formula (1).

[0044] (13) A preparation process of a fluorine compound represented bythe formula (13-1):

[0045] wherein Y¹ is an electrophilic substituent, b and d are integersof 1 to 5, and b+d≦6, comprising reacting an aromatic compound comprisedof a halogen atom except fluorine and represented by the formula (13):

[0046] wherein X₁ is a halogen atom except fluorine, and Y¹, b and d arethe same as in the formula (13-1), comprising reacting with the abovefluorinating agent represented by the formula (1).

[0047] (14) A preparation process of a fluorine containing olefiniccompound represented by the formula (25)

[0048] wherein R¹⁵ to R¹⁷ are a hydrogen atom or a lower alkyl grouphaving 1 to 3 carbon atoms and can be the same or different; and Z is—(Y)n—CHF₂—(Y)n—CH₂F or —CO—O—(Y)n—CH₂F, wherein Y is —CH₂— and n is 0or an integer of 1 to 5, comprises reacting a fluorinating agentrepresented by the formula (1) with olefinic compounds represented bythe formula (24)

[0049] wherein R¹⁵ to R¹⁷ are a hydrogen atom or a lower alkyl grouphaving 1 to 3 carbon atoms and can be the same or different; and X is—(Y)n—CHO, —(Y)n—CH₂OH, or —CO—O—(Y)n—CH₂OH, wherein Y is —CH₂— and n is0 or an integer of 1 to 5.

[0050] (15) A process according to one of the above 8 to 14 wherein thefluorinating agent is represented by the formula (2).

[0051] (16) A compound represented by the formula (2):

[0052] wherein a is an integer of 2 or 3, R⁵ and R⁶ are a substituted orunsubstituted, saturated or unsaturated lower alkyl group having 1 to 6carbon atoms and can be the same or different.

[0053] (17) A compound wherein the formula (2) is2,2-difluoro-1,3-dimethylimidazolidine represented by the formula (3):

[0054] (18) A compound wherein the formula (2) is2,2-difluoro-1,3-di-n-butylimidazolidine represented by the formula (4):

[0055] (19) A compound wherein the formula (5) isbis-di-n-butylamino-difluoromethane represented by the formula (7):

[0056] (20) A preparation process of a fluorinating agent represented bythe formula (1) in the above (1) comprising carrying out a halogenexchange reaction of a compound represented by the formula (14):

[0057] wherein X₂ and X₃ are a chlorine or a bromine atom, R¹ to R⁴ aresubstituted or unsubstituted, saturated or unsaturated alkyl group,substituted or unsubstituted aryl group, and can be the same ordifferent; R¹ and R² or R³ and R⁴ can bond to form a ring including anitrogen atom or a nitrogen atom and other hetero atoms; or R¹ and R³can bond to form a ring including a nitrogen atom or a nitrogen atom andother hetero atoms, with an alkali metal salt of a fluorine atom in aninert solvent.

[0058] (21) A preparation process of a fluorinating agent of the above(1) comprising reacting a compound represented by the formula (14) witha half equivalent of sodium fluoride, separating by filtration, andsuccessively reacting with potassium fluoride.

[0059] (22) A halogenating agent represented by the formula (15):

[0060] wherein X₄ and X₅ are a halogen atom and can be the same ordifferent except that both X₄ and X₅ are not fluorine atoms, chlorineatoms or bromine atoms; R¹ to R⁴ are a substituted or unsubstituted,saturated or unsaturated alkyl group or a substituted or unsubstitutedaryl group, and can be the same or different; R¹and R² or R³ and R⁴ canbond to form a ring including a nitrogen atom or a nitrogen atom andother hetero atoms; or R¹and R³ can bond to form a ring including anitrogen atom or a nitrogen atom and other hetero atoms.

[0061] (23) A halogenating agent according to the above (22) wherein thehalogenating agent represented by the formula (15) is represented by theformula (16):

[0062] wherein X₄ and X₅ are a halogen atom and can be the same ordifferent except that both X₄ and X₅ are not fluorine atoms, chlorineatoms or bromine atoms; a is an integer of 2 or 3, R⁵ and R⁶ are asubstituted or unsubstituted, saturated or unsaturated lower alkyl grouphaving 1 to 6 carbon atoms and can be the same or different.

[0063] (24) A halogenating agent according to the above (23) wherein thehalogenating agent represented by the formula (16) is2-halo-1,3-dimethylimidazolinium=halide represented by the formula (17):

[0064] wherein X₄ and X₅ are a halogen atom and can be the same ordifferent except that both X₄ and X₅ are not fluorine atoms, chlorineatoms or bromine atoms.

[0065] (25) A halogenating agent according to the above (23) wherein thehalogenating agent represented by the formula (16) is2-fluoro-1,3-dimethylimidazolinium=chloride represented by the formula(18):

[0066] (26) A halogenating agent according to the above (23) wherein thehalogenating agent represented by the formula (16) is2-fluoro-1,3-dimethylimidazolinium=bromide represented by the formula(19):

[0067] (27) A halogenating agent according to the above (23) wherein thehalogenating agent represented by the formula (16) is2-fluoro-1,3-dimethylimidazolinium=iodide represented by the formula(20):

[0068] (28) A halogenating agent according to the above (23) wherein thehalogenating agent represented by the formula (16) is2-chloro-1,3-dimethylimidazolinium=bromide represented by the formula(21):

[0069] (29) A halogenating agent according to the above (23) wherein thehalogenating agent represented by the formula (16) is2-chloro-1,3-dimethylimidazolinium=iodide represented by the formula(22):

[0070] (30) A halogenating agent according to the above (23) wherein thehalogenating agent represented by the formula (16) is2-iodo-1,3-dimethylimidazolinium=iodide represented by the formula (23):

[0071] (31) A preparation process of a halogenating agent represented bythe above formula (15) according to the above (21) comprising carryingout a halogen exchange reaction of a compound represented by the formula(14):

[0072] wherein X₂ and X₃ are a chlorine or bromine atom and R¹ to R⁴ arethe same as above, with an alkali metal salt of a fluorine atom,chlorine atom, bromine atom or iodine atom or a mixture thereof in aninert solvent.

[0073] (32) A preparation process of a halogen compound represented bythe formula (8-2):

R¹¹—X₅  (8-2)

[0074] wherein R₁₁ is a substituted or unsubstituted alkyl group and caninclude an unsaturated group therein and X₅ is a halogen atom,comprising reacting an alcoholic hydroxyl compound represented by theformula (8):

R¹¹—OH  (8)

[0075] wherein R¹¹ is the same as in the formula (8-2), with the abovehalogenating agent represented by the formula (15):

[0076] wherein X₄, X₅, and R¹ to R⁴ are the same as above.

[0077] (33) A preparation process of an acid halogenide speciesrepresented by the formula (12-2):

R¹⁵—COX₆  (12-2)

[0078] wherein R¹⁵ is a substituted or unsubstituted, saturated orunsaturated alkyl group or substituted or unsubstituted aryl group andX₆ is a halogen atom represented by X₄ or X₅ in the formula (15),comprising reacting a carboxylic acid compound represented by theformula (12):

R¹⁵—COOH  (12)

[0079] wherein R¹⁵ is the same as in the formula (12-2), with ahalogenating agent represented by the formula (15):

[0080] wherein X₄, X₅ and R¹ to R⁴ are the same as above.

[0081] (34) A preparation process of a fluorine compound represented bythe formula (10-2):

R¹²—CH (X₇)₂  (10-2)

[0082] wherein R¹² is a substituted or unsubstituted, saturated orunsaturated alkyl group, or a substituted or unsubstituted aryl group,and X₇ is a halogen atom represented by X₄ or X₅ in the formula (15) andtwo X⁷ can be the same or different, comprising reacting an aldehydecompound represented by the formula (10):

R¹²—CHO  (10)

[0083] wherein R¹² is the same as in the formula (10-2), with ahalogenating agent represented by the formula (15):

[0084] wherein X₄, X₅ and R¹ to R⁴ are the same as above.

[0085] (35) A preparation process of a halogen compound according to oneof the above 32 to 34 wherein the halogenating agent is represented bythe formula (17).

[0086] (36) A compound represented by the formula (15):

[0087] wherein X₄ and X₅ are a halogen atom and can be the same ordifferent except that both X₄ and X₅ are not fluorine atoms, chlorineatoms or bromine atoms; R¹ to R⁴ are a substituted or unsubstituted,saturated or unsaturated alkyl group or a substituted or unsubstitutedaryl group and can be the same or different; R¹ and R² or R³ and R⁴ canbond to form a ring including a nitrogen atom or a nitrogen atom andother hetero atoms; or R¹ and R³ can bond to form a ring including anitrogen atom or a nitrogen atom and other hetero atoms.

[0088] (37) A compound represented by the formula (16):

[0089] wherein X₄ and X₅ are same or different halogen atom except thatboth X₄ and X₅ are fluorine atom, chlorine atom or bromine atom, a is aninteger of 2 or 3, R⁵ and R⁶ are a substituted or unsubstituted,saturated or unsaturated lower alkyl group having 1 to 6 carbon atomsand can be the same or different.

[0090] (38) A halogenating agent according to the above (22) wherein thehalogenating agent is 2-halo-1,3-dimethylimidazolinium=haliderepresented by the formula (17):

[0091] wherein X₄, X₅ are the same as above.

[0092] (39) A compound, 2-fluoro-1,3-dinethylimidazolinium=chloriderepresented by the formula (18):

[0093] (40) A compound, 2-fluoro-1,3-dimethylimidazolinium=bromiderepresented by the formula (19):

[0094] (41) A compound, 2-fluoro-1,3-dimethylimidazolinium=iodiderepresented by the formula (20):

[0095] (42) A compound, 2-chloro-1,3-dimethylimidazolinium=bromiderepresented by the formula (21):

[0096] (43) A compound, 2-chloro-1,3-dimethylimidazolinium=iodiderepresented by the formula (22):

[0097] (44) A compound, 2-iodo-1,3-dimethylimidazolinium iodiderepresented by the formula (23):

[0098] (45) A preparation process of a halogenating agent represented bythe formula (15):

[0099] wherein R¹ to R⁴, X₄ and X₅ are the same as above, comprisingcarrying out a halogen exchange reaction of a compound represented bythe formula (1):

[0100] wherein R¹ to R⁴ are the same as above, with an alkali metal saltof chlorine a chlorine, bromine or iodine atom in the presence of aninert solvent.

[0101] The halogenating agent of the invention, fluorinating agent inparticular, is a fluorinating agent for a hydroxyl group, carboxyl groupand other oxygen containing functional groups of a compound, can behandled with safety and ease, and has high selectivity. Preparation ofthe fluorinating agent of the invention requires no specific equipmentand technique and can be carried out with economy. Further, ahalogenating agent obtained by substituting other halogen atom for thefluorine atom can also be applied to the preparation of compounds havinghalogen other than fluorine.

[0102] The halogenating agent of the invention, fluorinating agent inparticular, has eliminated problems of conventional techniques for thepreparation of the agent itself in industry and exhibits excellenteffects as a halogenating agent, fluorinating agent in particular, fororganic compounds particularly having an oxygen containing functionalgroup.

BRIEF DESCRIPTION OF THE DRAWING

[0103]FIG. 1 is an IR spectrum of 2,2-difluoro-1,3-dimethylimidazolidineprepared in Example 1.

DETAILED DESCRIPTION OF THE INVENTION

[0104] The fluorinating agent will be described.

[0105] The fluorinating agent of the invention is a compound representedby the above formula (1):

[0106] wherein R¹ to R⁴ are the same as above.

[0107] In the formula (1), R¹ to R⁴ are individually a substituted orunsubstituted, saturated or unsaturated alkyl group, or a substituted orunsubstituted aryl group, and can be the same or different; R¹ and R² orR³ and R⁴ can bond to form a ring including a nitrogen atom or anitrogen atom and other hetero atoms, or R¹and R³ can bond to form aring including a nitrogen atom or a nitrogen atom and other heteroatoms. R¹ to R⁴ are preferably an alkyl or aryl group having 1 to 6carbon atoms. The alkyl group can be straight or branched, and includesa methyl, ethyl, n-propyl, allyl, isopropyl, n-butyl, butenyl andn-hexyl group. The aryl group includes a phenyl group. R¹ to R⁴ can bethe same or different.

[0108] Further, R¹and R² or R³ and R⁴ can individually bond to form aheterocyclic ring which includes a nitrogen atom and has 3 to 5 carbonatoms, for example, a pyrrolidine ring and piperidine ring.

[0109] Moreover, R¹ and R³ can bond to form a five membered ring or sixmembered ring which includes two nitrogen atoms in the ring, forexample, an imidazolidine ring, imidazolidinone ring, pyrimidine ringand pyrimidinone ring.

[0110] Practical examples of the fluorinating agent which is representedby the formula (1) and preferably used in the invention include belowdescribed compounds. However, the scope of the invention is not limitedby the compounds shown below.

(1) EXAMPLES OF THE COMPOUND

[0111] Bis-dimethylamino-difluoromethane,bis-diethylamino-difluoromethane, bis-di-n-propylamino-difluoromethane,bis-di-isopropylamino-difluoromethane,bis-di-allylamino-difluoromethane, bis-di-n-butylamino-difluoromethane,bis-di-n-hexylamino-difluoromethane, bis-(1-pyrrolidyl)-difluoromethane,bis(1-piperidyl)-difluoromethane,2,2-difluoro-1,3-dimethyl-imidazolidine, 2,2-difluoro-1,3-diethyl-imidazolidine, 2 ,2-difluoro-1.3-di-n-propyl-imidazolidine, 2,2-difluoro-1,3-diisopropyl-imidazolidine,2,2-difluoro-1,3-diallyl-imidazolidine, 2,2-difluoro-1,3-di-n-butyl-imidazolidine,bis(N-methyl-N-phenyl)difluoromethane,2,2-difluoro-1,3-dimethyl-imidazolidine-4,5-dione, 2,2-difluoro-1,3-di-n-butyl-imidazolidine-4,5-dione, and2,2-difluoro-1,3-dimethyl-pyrimidine.

[0112] Particularly preferred agents are2,2-difluoro-1,3-dimethyl-imidazolidine represented by the formula (3),2,2-difluoro-1,3-di-n-butyl-dimidazolidine represented by the formula(4), bis-dimethylamino-difluoromethane represented by the formula (6),and bis-di-n-butylamino-difluoromethane represented by the formula (7).

[0113] The fluorinating agent represented by the formula (1) in theinvention can be prepared by the following process.

[0114] That is, a compound represented by the formula (14):

[0115] wherein X₂ and X₃ are a chlorine or a bromine atom and can be thesame or different; R¹ to R⁴ are substituted or unsubstituted, saturatedor unsaturated alkyl group, or a substituted or unsubstituted arylgroup, and can be the same or different; R¹and R² or R³ and R⁴ can bondto form a ring including a nitrogen atom or a nitrogen atom and otherhetero atoms; or R¹and R³ can bond to form a ring including a nitrogenatom or a nitrogen atom and other hetero atoms, is subjected to ahalogen exchange reaction with an alkali metal salt of fluorine in aninert solvent. The fluorinating agent can be safely obtained with ease.

[0116] Alkali metal salts of fluoride, which can be used are cesiumfluoride, rubidium fluoride, potassium fluoride and sodium fluoride.Preferred alkali metal salts of fluoride is a spray-dried potassiumfluoride for use in a fluorinating reaction. The grade is advantageousin view of economy and reaction efficiency.

[0117] X₂ and X₃ in the formula (14) are usually chlorine atoms.However, compounds having bromine atoms as X₂ and X₃ can also be used.

[0118] Practical compounds includetetraalkylchloroformamidinium=chloride,2-chloro-1,3-dialkylamidinium=chloride,tetraalkylbromoformamidinium=bromide, and2-bromo-1,3-dialkylamidinium=bromide.

[0119] The compound represented by the formula (14) used as raw materialfor preparing the compound represented by the formula (1) includes, forexample, tetraalkylurea, tetraalkylthiourea, N,N′-dialkylimidazolidinoneor N,N′-dialkylimidazolithione with a halogenating agent such asphosgene, thionyl chloride, thionyl bromide, phosphorus trichloride orphosphorus tribromide.

[0120] For example, 2-chloro-1,3-dimethylimidazolinium=chloride can beprepared with ease by way of the process described in Japanese Laid-OpenPatent SHO 59-25375. Practically, a solution of oxalyl chloride incarbon tetrachloride is dropwise added to 1,3-dimethylimidazolidinoneand reacted at room temperature to 60 for several to several dozenshours.

[0121] In the preparation of the fluorinating agent represented by theformula (1) in the invention, the amount of alkali metal salt offluorine for use in the halogen exchange reaction is preferably twoequivalents or more, more preferably 2 to 5 equivalents for the amountof tetraalkyl-haloformamidinium=halide. The amount less than 2equivalents leaves unexchanged halide. On the other hand, the amountexceeding 5 equivalents brings no remarkable improvement on the reactionyield.

[0122] No particular restriction is imposed upon the solvent of halogenexchange reaction so long as the solvent does not react withtetraalkyl-haloformamidinium=halide and generated compounds. Preferredsolvents include acetonitrile, dimethylformamide,1,3-dimethyl-2-imidazolidinone, dichloromethane and ethylene dichloride.

[0123] No particular limitation is put upon the amount of solvent in thereaction. However, the amount is preferably 1 to 10 times by weight forthe reacting substance in view of reaction efficiency and ease ofoperation. The reaction temperature is in the range of −20 to 150° C.,preferably 0 to 100° C. in view of reaction velocity and stability offormed product.

[0124] The halogen exchange reaction in the preparation of thefluorinating agent of the invention can also be carried out in thepresence of a phase transfer catalyst such as quaternary ammonium saltor quaternary alkylphosphonium salt. The reaction mixture of the halogenexchange reaction can be used as is for the next fluorinating reaction,or can also be used for the next halogenation reaction after filteringthe organic salt and distilling off the reaction solvent. The reactionproduct can also be isolated by distillation and used.

[0125] The fluorinating reaction using the fluorinating agent of theinvention can be carried out with extreme ease by using conventionalreaction equipment. For example, fluorinating reaction of carboxylicacid can be carried out by simply adding carboxylic acid to the reactionmixture of the halogen exchange reaction and reacting at roomtemperature for several hours. The corresponding fluoride of thecarboxylic acid compound can be thus obtained in high yield.

[0126] Fluorinating reaction of alcohol species can also be carried outby directly charging the alcohol compound to the reaction mass of thehalogen exchange reaction and reacting for several hours. Thecorresponding fluoride can be obtained in high yield.

[0127] The fluorinating reaction using the fluorinating agent of theinvention will hereinafter be illustrated in detail.

[0128] (1) Conventionally, direct conversion of an alcoholic hydroxylgroup into a fluorine group is a general-purpose, attractive process inthe synthetic method of monofluoro compounds.

[0129] Representative fluorinating agents which are effective for theconversion reaction include hydrogen fluoride which is an acid agent,pyridine-(HF)n, fluoroalkylamine (Yarovenko's reagent),diethylamine-hexafluoropropane adduct (hereinafter referred to simply asPPDA), SF₄ (a four valent sulfur compound), trifluorodiethylaminosulfur(hereinafter referred to simply as DAST) and PhPF₄ (a five valentphosphorus compound).

[0130] As mentioned above, hydrogen fluoride has disadvantage upondifficulty to handle because of toxicity, corrosivity and danger toexplosion in the reaction step and requirement for specific equipmentand technique. Pyridine-(HP)n has fluorination ability higher thanhydrogen fluoride itself. However, the ability is not so high ascompared with other fluorination agents.

[0131] The Yarovenko's reagent: fluoroalkylamine is a fluorinating agentobtained by addition of diethylamine to chlorotrifluoroethene. The agentcan fluorinate many kinds of primary and secondary alcohols under mildconditions in a solvent. However, the agent itself has low stability(can preserve for several days in a sealed, cold, dark place) [J. GenChe. USSR 19, 2125 (1959)].

[0132] PPDA is more frequently used because the agent is more stable,can be handled with more ease, and has similar reactivity.

[0133] Recently, N,N-diisopropyl-2-fluoroenamine has been reported as anew type fluorinating agent of fluoroamine base [Tetrahedron Lett., 30,3077 (1989)].

[0134] These reagents are useful for the fluorinating agents of analcoholic hydroxyl group. However, application to an industrial scale isdifficult to practice in view of complex procedures in synthesis andeconomy.

[0135] Additionally, DAST has similar problems as above also in thesubstitution of an alcoholic hydroxyl group for a fluorine group.

[0136] The fluorinating agent of the invention can be handled withsafety and ease and provide a fluorinated material in high selectivity.

[0137] The problems of conventional fluorinating agents in thefluorinating reaction of an alcoholic hydroxyl group can be eliminatedby using the fluorinating agent of the invention.

[0138] Preparation process of a fluorine compound from an alcoholichydroxyl compound, by use of a fluorinating agent of the invention, isas follows.

[0139] That is, an alcoholic hydroxyl compound represented by theformula (8):

R¹¹—OH  (8)

[0140] wherein R¹¹ is the same as above, is reacted with thefluorinating agent of the invention to prepare a fluorine compoundrepresented by the formula (8-1):

R¹¹—F  (8-1)

[0141] wherein R¹¹ is the same as above.

[0142] Representative alcohol compounds which have a hydroxyl group tobe fluorinated include, for example, methyl alcohol, ethyl, n-propyl,n-butyl, isobutyl, 2-methyl-1-butyl, n-amyl, neoamyl, isoamyl, n-hexyl,2- methyl-1-pentyl, 2-ethyl-1-butyl, n-heptyl, n-octyl, 2-ethlhexyl,n-nonyl, 3,5,5-trimethyl-1-hexyl, n-decyl, n-undecyl, n-dodecyl, allyl,methallyl, crotyl, benzyl, phenetyl, cinnamyl, propargyl,2-hydroxyethylacrylate, 2-hydroxyethylmethacrylate and other primaryalcohols; isopropyl, sec-butyl, sec-amyl, sec-isoamyl, 1-ethyl-1-propyl,4-methyl-2-pentyl, 1-methylhexyl, 1-ethylpentyl, 1-methylheptyl,cyclohexyl, 2-methylcyclohexyl, 3-methylcyclohexyl, 4-methylcyclohexyl,sec-phenetyl and other secondary alcohols; and tert-butyl alcohol,tert-amyl, 1-methylcyclohexyl,α-terpine and other tertiary alcohols.However, alcohol species is not limited to these compounds.

[0143] These alcohols represented by the formula (8) can individuallyprovide corresponding alkyl fluoride represented by the formula (8-1).

[0144] The amount of the fluorinating agent is usually 1 equivalent ormore for the alcoholic hydroxyl group. Hydrogen fluoride generated inthe reaction can be caught by using bases such as tertiary amine.

[0145] No particular restriction is imposed upon the solvent of reactionso long as the solvent does not react with the fluorinating agent andfluorine compounds formed by fluorination alcohol. Preferred solventsare acetonitrile, dichloromethane, ethylene dichloride,dimethylformamide and 1,3-dimethyl-2-imidazolidinone.

[0146] The reaction temperature depends upon the solvent and reactivityof the alcoholic hydroxyl group and is usually in the range of −40 to100° C., preferably −20 to 80° C. in view of reaction velocity andstabilityof tetraalkyl-fluoroformaminium-fluoride.

[0147] When a formed fluorine compound has a low boiling point or astructure liable to release hydrogen fluoride, the reaction temperatureis required to be as low as possible.

[0148] The fluoro compound formed by the reaction can be isolated withease from the reaction mixture by distillation or other means.

[0149] (2) Conversion of a phenolic hydroxyl group to a fluoro group isconsidered to be possible by application of conventionally knownfluorinating agents such as hydrogen fluoride, pyridine-(HF)n,fluoroalkylamine (Yarovenko's reagent), PPDA, SF₄ (four valent sulfurcompound), DAST, and PhPF₄ (five valent phosphorus compound). However,no example has been found at all on the application of thesefluorinating agents to such conversion reaction. Even though, thesefluorinating agents can be applied, the same problems as above willoccur in the reaction.

[0150] The fluorinating agent of the invention can also be favorablyused for the fluorinating reaction of a phenolic hydroxyl group.

[0151] Fluorinating reaction of thiophenol can also be carried out.However, the reaction is liable to accompany formation of disulfidecompounds as a by-product.

[0152] The fluorinating reaction of phenolic hydroxyl group canposition-selectively introduce a fluorine atom into the aromatic ring toprepare an aromatic fluorine compound. The reaction process is asfollows.

[0153] That is, a phenol compound or thiophenol compound represented bythe formula (9):

[0154] wherein Q, Y¹, b and c are the same as above, is reacted with thefluorinating agent of the invention to prepare a fluorinated phenolcompound represented by the formula (9-1):

[0155] wherein Y¹, b and c are the same as in the formula (9).

[0156] The phenolic compound which can be fluorinated has on thearomatic ring thereof one or more electrophilic substituents such asNO₂, —CN, —CF₃, —CHO, —COOH, and —CO—. Preferred phenolic compoundsinclude, for example, o-nitrophenol, p-nitrophenol, o-cyanophenol,p-cyanophenol, p-hydroxybenzaldehyde, o-hydroxybenzaldehyde,p-hydroxy-trifluoromethylbenzene, o-hydroxy-trifluoromethylbenzene,p-hydroxy-benzoicmethyl ester, o-hydroxy-benzoicmethyl ester,4,4′-dihydroxy-benzophenone, p-hydroxy-benzoic acid, o-nitrothiophenoland p-nitrothiophenol. However, phenolic and thiophenolic compounds arenot limited to these compounds.

[0157] These phenol or thiophenol compounds represented by the formula(9) provide corresponding fluorine compounds represented by the formula(9-1).

[0158] The amount of fluorinating agent is usually 1 equivalent or morefor a phenolic hydroxyl group. Hydrogen fluoride generated in thereaction can be caught with a base such as tertiary amine.

[0159] No particular restriction is imposed upon the solvent of thereaction so long as the solvent does not react with the fluorinatingagent and fluorine compounds generated by fluorination of phenols.Preferred solvents are acetonitrile, dichloromethane, ethylenedichloride, dimethylformamide and 1,3-dimethyl-2-imidazolidinone.

[0160] The reaction temperature depends upon the solvent and reactivityof phenolic hydroxyl group, and usually in the range of −0 to 150° C.,preferably 20 to 110° C. in view of reaction velocity and stability oftetraalkyl-fluoroformamidium=fluoride.

[0161] The fluorine compound formed by the reaction can be isolated withease from the reaction mixture by means of distillation.

[0162] (3) Direct conversion of formyl oxygen to a fluorine group isalso a useful method for preparing a fluorine compound.

[0163] As to a direct fluorination of a formyl group or a carbonyl groupof ketone, SF₄ and DAST have been known in the above fluorinatingagents. However, these fluorinating agents are unsatisfactory because ofa severe restriction due to the above mentioned reason.

[0164] The fluorinating agent of the invention can effectively achievefluorination of ketone groups. The process thereof is as follows.

[0165] That is, an aldehyde compound represented by the formula (10):

R¹²—CHO  (10)

[0166] wherein R¹² is a substituted or unsubstituted, saturated orunsaturated alkyl group or a substituted or unsubstituted aryl group, isreacted with a fluorinating agent of the invention to prepare thefluorine compound represented by the formula (10-1):

R¹²—CF₂  (10-1)

[0167] wherein R¹² is the same as in the formula (10).

[0168] Thus, the direct fluorination of formyl oxygen can be effectivelyachieved by using the fluorinating agent of the invention.

[0169] Exemplary compounds which have a fluorinatable formyl groupinclude, for example, formaldehyde, acetaldehyde, acrolein,methacrolein, propionaldehyde, butyraldehyde, isobutylaldehyde,valeraldehyde, isovaleraldehyde, hexaldehyde, heptaldehyde,octylaldehyde, nonylaldehyde, decylaldehyde and other aliphaticaldehydes; cyclohexanecarboxyaldehyde and other alicyclic aldehydes;benzaldehyde, p-nitrobenzaldehyde, anisaldehyde, phthalaldehyde,1-naphthoaldehyde and other aromatic aldehydes; and nicotinaldehyde,furfural and other heterocyclic aldehydes. However, aldehyde is notlimited to these compounds.

[0170] Fluorine compounds corresponding to these aldehyde compounds andhaving the formula (10-1) can be obtained.

[0171] The amount of the fluorinating agent is preferably 1 equivalentor more for a formyl group.

[0172] No particular restriction is imposed upon the solvent of thereaction so long as the solvent does not react with the fluorinatingagent, formyl compound and reaction product. Preferred solvents areacetonitrile, dichloromethane, chloroform, ethylene dichloride,1,2-dimethoxyethane, diethylene glycol dimethyl ether,N-methylpyrrolidinone, dimethylformamide and1,3-dimethyl-2-imidazolidinone.

[0173] The reaction temperature is preferably in the range of 0 to 150°C., more preferably 20 to 110° C.

[0174] The fluorine compound generated by the reaction can be isolatedwith ease by distillation from the reaction mixture. Further,bis-dialkylamino-difluoromethane can be recovered in the form oftetraalkylurea after finishing the reaction.

[0175] (4) Direct conversion of ketone oxygen into fluorine is anextremely useful method in the preparation of fluorine compounds, whenthe method is effective.

[0176] That is, a ketone compound having ketone group and represented bythe formula (11):

[0177] wherein R¹³ and R¹⁴ are the same as above, is reacted with afluorinating agent of the invention to prepare a fluorine compoundrepresented by the formula (11-1):

[0178] wherein R¹³ and R¹⁴ are the same as above.

[0179] Any compound having a ketone group in the molecule can be usedfor the fluorination reaction as a ketone compound. Such ketonecompounds are, for example, aryl ketone compounds and alkyl ketonecompounds. However, no restriction is put upon these ketone compounds.

[0180] The amount of bis-dialkylamino-difluoromethane as a fluorinatingagent is 1 equivalent or more for ketone.

[0181] No particular restriction is imposed upon the solvent for use inthe reaction so long as the solvent does not react with the fluorinatingagent, ketone compound and reaction product. Preferred solvents areacetonitrile, dichloromethane, chloroform, ethylene dichloride,1,2-dimethoxyethane, diethyleneglycol dimethyl ether,N-methylpyrrolidinone, dimethylformamide and1,3-dimethyl-2-imidazolidinone. The reaction temperature is preferablyin the range of 0 to 150° C., more preferably 20 to 110° C. The fluorinecompound formed by the reaction can be isolated with ease bydistillation from the reaction mixture. The fluorinating agent can berecovered in the form of a corresponding urea compound after finishingthe reaction.

[0182] (5) Fluorine substituted benzophenone prepared by fluorinatingreaction of benzophenone which is a ketone compound, is generally usedfor the material of polyether ether ketone and other polyether ketoneresins. Polyether ether ketone is a super engineering plastic andexcellent in thermal resistance, electrical insulation, sliding propertyand chemical resistance. Fluorine substituted benzophenone is also usedfor a raw material or an intermediate of flame retardant, pain killer,platelet coagulation inhibitor and thrombosis inhibitor and thus is animportant compound in the field of medicines and agricultural chemicals.

[0183] The fluorinating agent of the invention can directly fluorinate ahydroxy group of hydroxybenzophenone represented by the formula:

[0184] wherein m and n are an integer of 1 to 5 and are notsimultaneously zero, to obtain fluorine substituted benzophenone:

[0185] wherein m and n are the same as above.

[0186] Hydroxy substituted benzophenone which can be used in the processis 2-hydroxybenzophenone, 4-hydroxybenzophenone and other benzophenonederivatives having two phenyl groups which are arbitrarily selected froma 2-hydroxyphenyl, 4-hydroxyphenyl, 2,4-dihydroxyphenyl,2,5-dihydroxyphenyl, 2,6-dihydroxyphenyl and 2,4,6-trihydroxyphenylgroup.

[0187] The amount of a fluorinating agent is preferably 1 equivalent ormore for the hydroxy group and desirably 1 to 10 equivalents in view ofreaction efficiency unreacted hydroxy group remains when less than 1equivalent is used.

[0188] No particular restriction is imposed upon the solvent for use inthe reaction so long as the solvent does not react with the fluorinatingagent, hydroxy substituted benzophenone compound and reaction product,fluorine substituted benzophenone compound. Preferred solvents areacetonitrile, dichloromethane, chloroform, ethylenedichloride, glyme,diglyme, N-methylpyrrolidone, N,N-dimethylformamide and1,3-dimethyl-2-imidazolidinone.

[0189] The reaction temperature is preferably in the range of 0 to 150°C., more preferably 20 to 110° C. When the temperature is lower than 0°C., reaction velocity becomes slow and complex procedures are required.The reaction temperature exceeding 150° C. decreases stability of thefluorinating agent and tends to form by-products having a difluorinatedketone group. However, bis-fluorine substituted phenyl-difluoromethanecan be returned with ease to fluorine substituted benzophenone by meansof hydrolysis.

[0190] The fluorine compound formed by the reaction can be isolated withease from the reaction mixture by distillation, extraction and otherprocedures. The fluorinating agent used can be recovered in the form ofcorresponding urea after finishing the reaction.

[0191] (6) Conventionally, fluorinating agents which have been used forthe conversion reaction of carboxylic acid into carbonyl fluoride havebeen SF₄ a four valent sulfur compound, and trifluorodiethylaminosulfur(hereinafter referred to simply as DAST).

[0192] SF₄ can directly convert carboxyl group into trifluoromethylgroup. However, the converting reaction suffers from the defect thatselection of optimum conditions is difficult and the yield is not sohigh [Org React., 21, 1 (1974)]. Furthermore, SF₄ itself is toxic andcorrosive and has a problem of danger to explosion in the course ofreaction. Further, DAST can efficiently fluorinate a carboxyl group toprovide carboxylic acid fluoride, and is also useful as a fluorinatingagent for a hydroxyl group of primary, secondary and tertiary alcohol,carbonyl group and other oxygen containing functional groups. However,DAST has problems on requirement for a specific manufacturing facility,high price and high danger to explosion.

[0193] The fluorinating agent of the invention can eliminate theseproblems and a fluorinating reaction of carboxylic acid can be carriedout. Fluorine containing compounds thus obtained have been focused keenattention in recent years in the field of life science such as medicineand agricultural chemicals and also as a raw substance of functionalmaterials.

[0194] Carboxylic acid fluoride can be prepared by using thefluorinating agent of the invention as follows.

[0195] That is, a compound having a carboxylic acid group represented bythe formula (12):

R¹⁵—COOH  (12)

[0196] wherein R¹⁵ is the same as above, is reacted with a fluorinatingagent of the invention to prepare acid fluoride represented by theformula (12-1):

R¹⁵—COF  (12-1)

[0197] wherein R¹⁵ is the same as above.

[0198] Representative carboxylic acids which can be used for thefluorination reaction include, for example, formic acid, acetic,propionic, butanoic, isobutanoic, pentanoic, 3-methyl-butanoic, pivalic,hexanoic, heptanoic, octanoic, nonanoic, decanoic, lauric, myristic,palmitic, stearic, phenylacetic, diphenylacetic, acetoacetic,phenylpropionic, cinnamic, oxalic, malonic, succinic, methylsuccinic,1,5-pentanedicarboxylic, adipic, 1,7-heptane-dicarboxylic, suberic,azeloic, sebacic, dodecanedicarboxylic, eicosandicarboxylic and otheraliphatic monocarboxylic and dicarboxylic acids; cyclohexanecarboxylic,1-methyl-1-cyclohexanecarboxylic, 2-methyl-1-cyclohexanecarboxylic,3-methyl-1-cyclohexanecarboxylic, 1,3-dicyclohexanedicarboxylic,1,4-dicyclohexanedicarboxylic and other alicyclic mono- anddi-carboxylic acids; benzoic, o-toluic, m-toluic, p-toluic,4-isopropylbenzoic, 4-tert-butylbenzoic, o-methoxybenzoic,m-methoxybenzoic, p-methoxybenzoic, dimethoxybenzoic, trimethoxybenzoic,o-nitrobenzoic, m-nitrobenzoic, p-nitrobenzoic, phthalic, isophthalic,terephthalic and other aromatic monocarboxylic and dicarboxylic acids;and indole-2-carboxylic, indole-3-carboxylic, nicotinic and otherheterocyclic carboxylic acids. However, no restriction is put upon thesecompounds. Acid fluoride compounds represented by the formula (12-1) canbe individually obtained from corresponding carboxylic acid.

[0199] The amount of fluorinating agent is usually 1 equivalent or morefor the carboxyl group.

[0200] The reaction is usually carried out in a solvent. No particularrestriction is imposed upon the solvent so long as the solvent does notreact with the fluorinating agent used and carboxylic acid fluorideformed. Preferred solvents are acetonitrile, dichloromethane,ethylenedichloride, dimethylformamide and1,3-dimethyl-2-imidazolidinone.

[0201] The reaction temperature depends upon the solvent and reactivityof the carboxyl group and is usually in the range of −40 to 100° C.,preferably −20 to 80° C. in view of the reaction velocity and depressionof by-products. Carboxylic acid fluoride formed by the reaction can beisolated with ease from reaction mixture by distillation.

[0202] (7) Fluorination by way of a halogen exchange reaction

[0203] A process for preparing a fluorine compound from a halogencompound except fluorine compound by way of a halogen exchange reactionusing metal fluoride, is a classical process. Other fluorinating agentswhich have been used are tetrabutylammonium fluoride (TBAF), TBAF HF,70% HF-pyridine, andtris(dimethylamino)sulfonium-difluorotrimethylsilicate (TASF). However,TBAF is hygroscopic and decomposes at high temperature, and thus must behandled with caution. TASF has a problem of high price.

[0204] Application of the fluorinating agent of the invention enableseffective syntheses of fluorinated compounds by a halogen exchangereaction. The reaction can exchange a halogen group of a compound with afluorine group by using the fluorinating agent of the invention.

[0205] Aliphatic or aromatic compounds having a halogen group other thana fluorine group can be used for the object compound of the fluorinatingreaction. However, a halogen group directly bonded to the aromatic ringcan be more efficiently fluorinated with the fluorinating agent of theinvention when one or more electrophilic substituents (for example, anitro, carbonyl, cyano, trifluoromethyl or carboxyl group) are directlybonded to the aromatic ring.

[0206] A preferred example of the exchange reaction is a process forreacting an aromatic compound which has a halogen atom except fluorineand is represented by the formula (13):

[0207] wherein X₁ is a halogen atom except fluorine, d is an integer of1 to 5, Y¹ is an electrophilic substituent, b is an integer of 1 to 5,and b+d≦6, with the fluorinating agent of the invention to prepare afluorine compound represented by the formula (13-1):

[0208] wherein Y¹, b and d are the same as in the formula (13).

[0209] Exemplary compounds which have a halogen group to be replaced bya fluorine group include, for example, 2,4-dinitrochlorobenzene,4-chloronitrobenzene, 2-chloronitrobenzene, 2,3,4,5,6-pentachloronitrobenzene, 3,4,5,6-tetrachlorophthalic anhydride,3,4,5,6-tetrachlorophthalyl chloride,4,4′-dichloro-3,3′-dinitrobenzophenone, 4-chloro-trifluoromethylbenzene,4-chloro-cyanobenzene and 4-bromobenzaldehyde. However, halogencompounds are not limited to the above compounds.

[0210] These halogen compounds individually provide a correspondingfluorine compounds represented by the formula (13-1).

[0211] The amount of the fluorinating agent is 1 equivalent or more,preferably 1 to 10 equivalents for a halogen group to be replaced byfluorine.

[0212] No particular restriction is imposed upon the solvent so long asthe solvent does not react with the fluorinating agent, compounds havinghalogen groups and reaction products. Preferred solvents areacetonitrile, dichloromethane, chloroform, ethylene dichloride,1,2-dimethyoxyethane, diethylene glycol dimethyl ether,N-methylpyrrolidinone, dimethylformamide and 1,3-dimethyl-2-imidazolidinone.

[0213] The reaction temperature is preferably in the range of 0 to 150°C., more preferably 20 to 110° C.

[0214] The fluorine compound formed by the reaction can be isolated withease from the reaction mixture by means of distillation. Thefluorinating agent can be recovered after hydrolysis in the form ofcorresponding urea.

[0215] (8) The fluorinating agent of the invention can be suitably usedfor preparing fluorine containing olefinic compounds. That is, thepreparation process of fluorine containing olefinic compoundsrepresented by the formula (25):

[0216] wherein R¹⁵ to R¹⁷ are a hydrogen atom or a lower alkyl grouphaving to 3 carbon atoms and can be the same or different; and Z is—(Y)n—CHF₂, —(Y)_(n)—CHF₂ or —CO—O—(Y)n CH₂F, wherein Y is —CH₂— and nis 0 or an integer of 1 to 5, comprises reacting a fluorinating agentrepresented by the formula (1) with olefinic compounds represented bythe formula(24)

[0217] wherein R¹⁵ to R¹⁷ are a hydrogen atom or a lower alkyl grouphaving 1 to 3 carbon atoms and can be the same or different; and X is—(Y)n—CHO, —(Y)n—CH₂OH, or —CO—O—(Y)n—CH₂OH wherein Y is —CH₂— and n is0 or an integer of 1 to 5.

[0218] No particular restriction is imposed upon the olefins used in theinvention.

[0219] Preferred olefinic compounds which can be used include an olefinspecies having an aldehyde group or the end of the molecule (the formula26), an olefin species having a hydroxyl group on the molecular end (theformula 27) and olefinic ester having a hydroxyl group on the molecularend (the formula 28).

[0220] wherein R¹⁵ to R¹⁷ and Y are the same as above.

[0221] These olefinic compounds are fluorinated the —CHO group into the—CHF₂ group and the —CH₂OH group into the CH₂F group, respectively, andindividually provide the fluorine containing olefinic compounds whichcorrespond to the above formulas (26), (27) and (28).

[0222] On the fluorination reaction between the fluorinating agentrepresented by the formula (1) and the olefinic compound having analdehyde group represented by the formula (26), the amount ofbis-dialkylamino-difluoromethane is preferably 1 equivalent or more forthe aldehyde group. when the fluorination reaction is carried out on theolefinic compounds having a hydroxyl group represented by the formula(27) or (28). The amount of bis-dialkylamino-difluoromethane ispreferably 1 equivalent or more for the hydroxyl group.

[0223] No particular restriction is imposed upon the solvent so long asthe solvent is inert and does not react withbis-dialkylamino-difluoromethane and olefinic compounds having analdehyde group or a hydroxy group. Preferred solvents are acetonitrile,dichloromethane, chloroform, ethylene dichloride, glyme, diglyme,N-methyl-pyrrolidinone, dimethylformamide and1,3-dimethyl-2-imidazolidinone.

[0224] No particular limitation is imposed upon the amount of the amountof the solvent. However, the amount is preferably 1 to 10 times byweight for the substrate in view of reaction efficiency and operationability. On carrying out the reaction, base such as tertiary amine ispreferably added in order to capture generated hydrogen fluoride.

[0225] No particular limitation is put upon the reaction temperature.However, in the case of an olefin compound having an aldehyde group, thetemperature is in the range of 0 to 150° C., preferably 20 to 110° C. inview of reaction velocity and stability of product. In the case of anolefin compound having a hydroxyl group, the temperature is in the rangeof −40 to 100° C., preferably −20 to 80° C. When elimination of hydrogenfluoride is a competitive reaction, the reaction is preferably carriedout at low temperature as possible.

[0226] The fluorine compound formed by the reaction can be removed withease from the reaction mixture by means of distillation.Bis-dialkylamino-difluoromethane can be recovered in the form oftetraalkylurea after finishing the reaction.

[0227] (9) The fluorinating agent of the invention can be applied to thepreparation of fluorine containing diaminobenzophenone and fluorinecontaining diamino-diphenylmethane which are useful for a monomer ofpolyimide.

[0228] That is, below described compounds can be prepared from3,3′-dinitro-4,4′-dichlorobenzophenone which is available with ease inindustry.

[0229] Use of the fluorinating agent in the invention enables to preparedesired fluorine compounds with suitable conditions. As shown above bythe formulas (a) to (f), 3,3′-dinitro-4,4′-dichlorobenzophenone (a) isused for preparing 4-chloro-4′-fluoro-3,3′-dinitrobenzophenone (b),bis(3-nitro-4-chlorophenyl)difluoromethane (c),3,3′-dinitro-4,4′-difluorobenzophenone (d),4-chloro-4′-fluoro-3,3′-dinitrophenyldifluoromethane (e),andbis(3-nitro-4-fluorophenyl)difluoromethane (f).

[0230] A compound having larger numbers of the substituted fluorinegroups can be obtained with increase in the mol ratio of thefluorinating agent to 3,3′-dinitro-4,4′-dichloro benzophenone. Further,a compound having a large number of the fluorine group can also beobtained by preparing a compound having a less number of the fluorinegroup and reacting the compound with the fluorinating agent.

[0231] For example, the fluorine compound (f) can be prepared by using 2equivalent or more fluorinating agent for the raw material compound (a).

[0232] The reaction shows that the direct conversion of ketone oxygen inthe above (4) into fluorine and the fluorinating reaction by way of anexchange reaction of halogen which is substituted on the aromatic ringin the above (7) can progress with ease by the fluorinating agent of theinvention. The solvent, reaction temperature and other conditions are inaccordance with the reaction conditions in the above (4) and (7).

[0233] The reaction shown in (8) is one of the preferred embodiments forusing the halogenating agent of the invention in the halogenation ofcompounds having a ketone or halogen group.

[0234] Next, the halogenating agent of the formula (15) will beillustrated.

[0235] The halogenating agent of the invention is a compound representedby the formula (15):

[0236] In the formula (15), X₄ and X₅ are the same or different halogenatoms except that both X₄ and X₅ are not simultaneously fluorine atoms,chlorine atoms or bromine atoms.

[0237] The combination of X₄ and X₅ are F—Cl, F—Br, F—I, Cl—Br, Cl—I andI—I. Additionally, when halogen atoms of X₄ and X₅ are different, theatom having a lower atomic weight is liable to form a covalent bond andthe atom having a higher atomic weight tends to form an ion pair.

[0238] R¹ to R⁴ are same or different, substituted or unsubstitutedsaturated or unsaturated alkyl group or substituted or unsubstitutedaryl group. R¹ and R² or R³ and R⁴ can bond to form a ring including anitrogen atom or a nitrogen atom and other hetero atoms. R¹ and R³ canbond to form a ring including a nitrogen atom or a nitrogen atom andother hetero atoms. Preferred alkyl or aryl group has preferably 1 to 6carbon atoms. Alkyl group is straight or branched, that is, a methylgroup, ethyl, n-propyl, allyl, isopropyl, n-butyl, butenyl, n-hexyl orphenyl group and can be the same or different.

[0239] Further, R¹ and R² or R³ and R⁴ can respectively bond to form aheterocyclic ring having a nitrogen atom and 3 to 5 carbon atoms.Examples of such rings are pyrrolidine ring and piperidine ring.

[0240] Further, R¹and R³ can bond to form a five- or six-memberedheterocyclic ring including two nitrogen atoms such as an imidazolidinering, imidazolidinone ring, pyrimidine ring and pyrimidinone ring.

[0241] Preferred practical examples of the halogenating agentrepresented by the formula (15) include following compounds. However,the scope of the invention is not restricted by these exemplifiedhalogenating agents.

[0242] Exemplary chlorinating agents include:

[0243] tetramethyl-2-fluoroformamidinium=chloride,

[0244] tetraethyl-2-fluoroformamidinium=chloride,

[0245] tetra-n-propyl-2-fluoroformamidinium=chloride,

[0246] tetraisopropyl-2-fluoroformamidinium=chloride,

[0247] tetra-n-butyl-2-fluoroformamidinium=chloride,

[0248] tetra-n-pentyl-2-fluoroformamidinium=chloride,

[0249] tetra-n-hexyl-2-fluoroformamidinium=chloride,

[0250] 2-fluoro-1,3-dimethylimidazolinium=chloride,

[0251] 2-fluoro-1,3-diethylimidazolinium=chloride,

[0252] 2-fluoro-1,3-di-n-propylimidazolinium=chloride,

[0253] 2-fluoro-1,3-di-n-butylimidazolinium=chloride,

[0254] 2-fluoro-1,3-di-n-pentylimidazolinium=chloride,

[0255] 2-fluoro-1,3-di-n-hexylimidazolinium=chloride,

[0256] N,N-dimethyl-N′,N′-methylphenyl-fluoroformamidinium=chloride, and

[0257] fluoro-bis(1-piperidyl)methylium=chloride.

[0258] Exemplary brominating agents include:

[0259] tetramethyl-2-fluoroformamidinium=bromide,

[0260] tetraethyl-2-fluoroformamidinium=bromide,

[0261] tetra-n-propyl-2-fluoroformamidinium=bromide,

[0262] tetraisopropyl-2-fluoroformamidinium=bromide,

[0263] tetra-n-butyl-2-fluoroformamidinium=bromide,

[0264] tetra-n-pentyl-2-fluoroformamidinium=bromide,

[0265] tetra-n-hexyl-2-fluoroformamidinium=bromide,

[0266] 2-fluoro-1,3-dimethylimidazolinium=bromide,

[0267] 2-fluoro-1,3-diethylimidazolinium=bromide,

[0268] 2-fluoro-1,3-di-n-propylimidazolinium=bromide,

[0269] 2-fluoro-1,3-di-n-butylimidazolinium=bromide,

[0270] 2-fluoro-1,3-di-n-pentylimidazolinium=bromide,

[0271] 2-fluoro-1,3-di-n-hexylimidazolinium=bromide,

[0272] N,N-dimethyl-N′, N′-dimethylphenyl-fluoroformamidinium=bromide,

[0273] fluoro-bis(1-piperidyl)methylium=bromide,

[0274] tetramethyl-2-chloroformamidinium=bromide,

[0275] tetraethyl-2-chloroformamidinium=bromide,

[0276] 2-chloro-1,3-dimethylimidazolinium=bromide and

[0277] 2-chloro-1,3-diethylimidazolinium=bromide.

[0278] Exemplary iodinating agents include:

[0279] tetramethyl-2-fluoroformamidinium=iodide,

[0280] tetraethyl-2-fluoroformamidinium=iodide,

[0281] tetra-n-propyl-2-fluoroformamidinium=iodide,

[0282] tetraisopropyl-2-fluoroformamidinium=iodide,

[0283] tetra-n-butyl-2-fluoroformamidinium=iodide,

[0284] tetra-n-pentyl-2-fluoroformamidinium=iodide,

[0285] tetra-n-hexyl-2-fluoroformamidinium=iodide,

[0286] 2-fluoro-1,3-dimethylimidazolinium=iodide,

[0287] 2-fluoro-1,3-diethylimidazolinium=iodide,

[0288] 2-fluoro-1,3-di-n-propylimidazolinium=iodide,

[0289] 2-fluoro-1,3-di-n-butylimidazolinium=iodide,

[0290] 2-fluoro-1 , 3-di-n-pentylimidazolinium=iodide,

[0291] 2-fluoro-1,3-di-n-hexylimidazolinium=iodide,

[0292] N,N-dimethyl-N′, N′-dimethylphenyl-fluoroformamidinium=iodide,

[0293] fluoro-bis(1-piperidyl)methylium=iodide,

[0294] tetramethyl-2-chloroformamidinium=iodide,

[0295] tetraethyl-2-chloroformamidinium=iodide,

[0296] 2-chloro-1,3-dimethylimidazolinium=iodide,

[0297] 2-chloro-1,3-diethylimidazolinium=iodide,

[0298] tetramethyl-2-iodoformamidinium=iodide,

[0299] tetraethyl-2-iodoformamidinium=iodide,

[0300] 2-iodo-1,3-dimethylimidazolinium=iodide,

[0301] 2-iodo-1,3-diethylimidazolinium=iodide.

[0302] Tetraalkyl-fluoroformamidinium=halide is a preferable compoundand can react with alcohol in a very mild condition to obtain a halogencompound resulting from exchanging the counter ion (X₅) with analcoholic hydroxyl group on the compound represented by the formula(15).

[0303] Particularly preferred compounds are:

[0304] 2-fluoro-1,3-dimethylimidazolinium=chloride represented by theformula (18):

[0305] 2-fluoro-1,3-dimethylimidazolinium=bromide represented by theformula (19):

[0306] 2-fluoro-1,3-dimethylimidazolinium=iodide represented by theformula (20):

[0307] 2-chloro-1,3-dimethylimidazolinium=bromide represented by theformula (21):

[0308] 2-chloro-1,3-dimethylimidazolinium=iodide represented by theformula (22):

[0309] 2-iodo-1,3-dimethylimidazolinium=iodide represented by theformula (23):

[0310] These halogenating agents can be applied to the above varioushalogenating reactions of the invention.

[0311] Desired halogen compounds can be obtained by carrying out thedesired halogenating reaction with a suitable halogenating agentaccording to the above reaction, respectively.

[0312] For example, halogenating of an alcoholic hydroxyl group withthese halogenating agents can selectively provide a halogen compound ofthe counter (X₅) on the formula (15).

[0313] That is, an alcoholic hydroxyl group containing compoundrepresented by the formula (8):

R¹¹—OH  (8)

[0314] wherein R¹¹ is a substituted or unsubstituted alkyl group and caninclude an unsaturated group therein, is reacted with the halogenatingagent represented by the formula (15):

[0315] wherein X₄, X₅, and R¹ to R⁴ are the same as above, to prepare ahalogen compound represented by the formula (8-2):

R¹¹—X₅  (8-2)

[0316] wherein R¹¹ is a substituted or unsubstituted alkyl group and caninclude an unsaturated group therein and X₅ is a halogen atom.

[0317] Exemplary alcoholic hydroxyl compounds which can be utilized forthe reaction include methyl alcohol, ethyl, n-propyl, n-butyl, isobutyl,2-methylbutyl, n-amyl, neoamyl, isoamyl, n-hexyl, 2-methylpentyl,2-ethylbutyl, n-nonyl, 3,5,5-trimethylhexyl, n-decyl, n-undecyl,n-dodecyl, allyl, methallyl, crotyl, benzyl, phenetyl, cinnamyl,propargyl alcohol and other primary alcohols ; and isopropyl, sec-butyl,sec-amyl, sec-isoamyl, 1-ethylpentyl, 1,3-dimethylbutyl, 1-methylhexyl,1-ethylpentyl, 1-ethylpropyl, 4-methyl-2-pentyl, 1-methylhexyl,1-ethylpentyl, 1-methylheptyl, cyclohexyl, 2-methylcyclohexyl,3-methylcyclohexyl, 4-methylcyclohexyl, sec-phenetyl alcohol and othersecondary alcohols ; and tert-butyl, tert-amyl, 1-methylcyclohexyl,a-terpin alcohol and other tertiary alcohols However, alcoholic hydroxylcompounds are not restricted to these compounds.

[0318] The amount of the halogenating agent is usually 1 equivalent ormore for an alcoholic hydroxyl group. No particular restriction isimposed upon the solvent so long as the solvent does not react with thereaction substrate, reaction agent and reaction product. The solvent ispreferably acetonitrile, dichloromethane, ethylene dichloride, glyme,diglyme, dimethylformamide, 1,3-dimethyl-2-imidazolidinone, benzene,toluene and hexane.

[0319] The reaction temperature is usually −40 to 100° C., preferably−20 to 80° C. Formed products can be isolated with ease from thereaction mixture by means of distillation.

[0320] Further, the reaction can be carried out in the presence of ahydrogen halogenide capturing agent, base and acid catalyst so long asthese materials give no adverse effect on the halogenating agentrepresented by the formula (15), oxygen containing functional compoundand reaction product.

[0321] The halogen compound formed by the reaction can be isolated withease from the reaction mixture by means of distillation. When thecompound represented by the formula (15) remains unreacted, generatedhydrogen halogenide can be caught by addition of sodium hydrogencarbonate.

[0322] Furthermore, the halogenating agent represented by the formula(15) can be recovered in the form of corresponding urea after finishingthe reaction.

[0323] Carboxylic acid halogenides represented by the formula (12-2):

R¹⁵—COX₆  (12-2)

[0324] wherein R¹⁵ is a substituted or unsubstituted, saturated orunsaturated alkyl group or substituted or unsubstituted aryl group andX₆ is a halogen atom represented by X₄ or X₅ in the formula (15) whichcan prepared by reacting a carboxylic acid compound represented by theformula (12):

R¹⁵—COOH  (12)

[0325] wherein R¹⁵ is the same as in the formula (12-2), with the abovehalogenating agent represented by the formula (15).

[0326] The resulting carboxylic acid halide group has a halogen atomwhich individually corresponds to X₄ and X₅ in the formula (15). When X₄is F and X₅ is Br on the formula (15) of the halogenating agent,carboxylic acid bromide, carboxylic acid fluoride and carboxylic acidanhydride are formed, and carboxylic acid fluoride has the highestselectivity.

[0327] When X₄ is F and X₅ is I on the formula (15) of the halogenatingagent, carboxylic acid fluoride and carboxylic acid anhydride areformed, and carboxylic acid fluoride has the higher selectivity.Formation of carboxylic acid iodide cannot be confirmed.

[0328] Representative compounds which have a carboxyl group and can beused for the reaction include, for example, formic acid, acetic,propionic, butanoic, isobutanoic, pentanoic, 3-methylbutanoic, pivalic,hexanoic, heptanoic, octanoic, nonanoic, decanoic, lauric, myristic,palmitic, stearic, phenylacetic, diphenylacetic, acetoacetic,phenylpropionic, cinnamic, oxalic, malonic, succinic, methylsuccinic,1,5-pentanedicarboxylic, adipic, 1,7-heptanedicarboxylic, suberic,azelaic, sebacic, dodecanedicarboxylic, eicosanedicarboxylic acid andother aliphatic monocarboxylic and dicarboxylic acids;cyclohexylcarboxylic, 1-methyl-1-cyclohexylcarboxylic,2-methyl-1-cyclohexylcarboxylic, 3-methyl-1-cyclohexylcarboxylic,1,3-dicyclohexyldicarboxylic, 1,4-dicyclohexylcarboxylic acid and otheralicyclic monocarboxylic and dicarboxylic acids; benzoic, o-toluic,m-toluic, p-toluic, 4-isopropylbenzoic, 4-tert-butylbenzoic,o-methoxybenzoic, m-methoxybenzoic, p-methoxybenzoic, dimethoxybenzoic,trimethoxybenzoic, o-nitrobenzoic, m-nitrobenzoic, p-nitrobenzoic,phthalic, isophthalic, terephthalic acid and other aromaticmonocarboxylic and dicarboxylic acids; indole-2-carboxylic,indole-3-carboxylic, nicotinic acid and other heterocyclic carboxylicacids. However, carboxyl compounds are not limited to these compounds.

[0329] The amount of halogenating agents is usually 1 equivalent or morefor the carboxyl group. No particular restriction is imposed upon thesolvent so long as the solvent does not react with reaction substrates,reaction agents and formed products. Preferred solvents areacetonitrile, dichloromethane, ethylene-dichloride, glyme, diglyme,dimethylformamide, 1,3-dimethyl-2-imidazolidinone, benzene and toluene.

[0330] The reaction temperature is usually −40 to 100° C., preferably−20 to 80° C. Formed products can be isolated with ease from thereaction mixture by means of distillation.

[0331] Further, a hydrogen halogenide capturing agent, base and acidcatalyst can be added to the reaction system so long as these materialsgive no adverse effect on the halogenating agent represented by theformula (15), oxygen containing functional compound and reactionproduct.

[0332] The halogen compound formed by the reaction can be isolated withease from the reaction mixture by means of distillation.

[0333] When the compound represented by the formula (15) remainsunreacted, generated hydrogen halogenide can be caught by addition ofsodium hydrogen carbonate.

[0334] Furthermore, the halogenating agent represented by the generalformula (15) can be recovered in the form of corresponding urea afterfinishing the reaction.

[0335] Fluorine compound represented by the formula (10-2):

R¹²—CH (X₇)₂  (10-2)

[0336] wherein R² is a substituted or unsubstituted, saturated orunsaturated alkyl group or a substituted or unsubstituted aryl group andX₇ is the halogen atom represented by X₄ or X₅ in the formula (15) andtwo X⁷'s are not simultaneously same, can be prepared by reacting analdehyde compound represented by the formula (10):

R¹²—CHO  (10)

[0337] wherein R¹² is the same as in the formula (10-2), with ahalogenating agent the above halogenating agent.

[0338] When a halogenating agent having F on X₄ and Cl on X₅ in theformula (15) is used for halogenation of a formyl group, conversion ofthe formyl group into a chlorofluoromethyl group and dichloromethylgroup is observed. In the case, the chlorofluoromethyl group can beobtained in higher selectivity.

[0339] Exemplary compounds having a halogenatable formyl group include,for example, form-aldehyde, aceto, propio, butyl, isobutyl, valer,isovaler, hexa, hept, octyl, nonyl, decylaldehyde and other aliphaticaldehydes; benz, p-nitrobenz, anisic, phthalic, naphthoaldehyde andother aromatic aldehyde; cyclohexanecarboxyaldehyde and other alicyclicaldehydes; and nicotinic aldehyde, furfural and other heterocyclicaldehydes. However, aldehyde compounds are not limited to thesecompounds.

[0340] The amount of halogenating agent is usually 1 equivalent or morefor a formyl group. No particular restriction is imposed upon thesolvent so long as the solvent dose not react with reaction substrates,reaction agents and reaction products. Preferred solvents areacetonitrile, dichloromethane, ethylene dichloride, glyme, diglyme,dimethylformamide, 1,3-dimethyl-2-imidazolidinone, benzene and toluene.

[0341] The reaction temperature is usually 0 to 150° C., preferably 20to 110° C. The reaction product can be isolated with ease from thereaction mixture by means of distillation.

[0342] Further, the reaction can be carried out in the presence of ahydrogen halogenide capturing agent, base and acid catalyst so long asthese materials give no adverse effect on the halogenating agentsrepresented by the formula (15), oxygen containing functional compoundsand reaction products.

[0343] The halogenated compounds formed by the reaction can be isolatedwith ease from the reaction mixture by means of distillation. When thehalogenating agent represented by the formula (15) remains unreacted,generated hydrogen halogenide can be caught by addition of sodiumhydrogen carbonate.

[0344] Further, the halogenating agent represented by the formula (15)can be recovered in the form of corresponding urea after finishing thereaction.

[0345] These halogenating agents represented by the formulas (15) to(17) can be safely prepared with ease by carrying out a halogen exchangereaction of a compound represented by the formula (14):

[0346] wherein X₂ and X₃ are a chlorine or bromine atoms; R¹ to R⁴ are asubstituted or unsubstituted, saturated or unsaturated alkyl group, or asubstituted or unsubstituted aryl group and can be the same ordifferent; R¹ and R² or R³ and R⁴ can bond to form a ring including anitrogen atom or a nitrogen atom and other hetero atoms ; or R¹ and R³can bond to form a ring including a nitrogen atom or a nitrogen atom andother hetero atoms, with an alkali metal salt of desired halogen in aninert solvent.

[0347] The compound represented by the formula (15) can be used asintact for a chlorinating agent or a brominating agent. However, inorder to obtain a halogenating agent having high reactivity,tetraalkyl-2-fluoroformamidinium=chloride is prepared by reacting withan alkali metal salt of fluorine such as cesium fluoride, rubidiumfluoride, potassium fluoride or sodium fluoride and can be used as achlorinating agent or a brominating agent.

[0348] In order to prepare a brominating agent from a compound havingchlorine atoms on the positions of X₂ and X₃, sodium bromide, potassiumbromide and other alkali metal salts of bromine can be used.

[0349] When an iodating agent is desired, cesium iodide, rubidiumiodide, potassium iodide and sodium iodide can be used.

[0350] The halogenating agent represented by the formula (15) isprepared from the compound represented by the formula (14) which isprepared as mentioned above.

[0351] On the preparation of a halogenating agent represented by theformula (15) in the invention, the amount of the alkali metal salt ofhalogen used for the halogen exchange reaction is preferably 2equivalents or more, more preferably 2 to 5 equivalents for the compoundrepresented by the formula (14). When the amount is less than 2equivalents, unexchanged chloride remains unsatisfactorily. On the otherhand, the amount exceeding 5 equivalents does not improve the yield somuch.

[0352] No particular restriction is imposed upon the solvent used forthe halogen exchange reaction so long as the solvent does not react withthe compound represented by the formula (14) and reaction product.Preferred solvents are acetonitrile, dimethylformamide,1,3-dimethyl-2-imidazolidinone, dichloromethane and ethylene dichloride.

[0353] No particular limitation is put upon the amount of the solvent.However, in view of reaction efficiency and operation ability, preferredamount is 1 to 10 times by weight for the reaction substrate.

[0354] The reaction temperature is usually in the range of −20 to 150°C., preferably 0 to 100° C. in view of reaction velocity and stabilityof the formed compound. The iodating agent is prepared preferably in therange of 0 to 80° C. in a nitrogen atmosphere under light shielding inorder to inhibit oxidation of the iodating agent.

[0355] The above halogen exchange reaction can also be carried out inthe coexistence of a phase transfer catalyst such as quaternary alkylammonium salt and quaternary alkyl phosphonium salt. The reactionmixture containing the resultant halogenating agent represented by theformula (15) can be used for the next halogenating reaction as is orafter filtering the inorganic salt and distilling off the solvent.

[0356] The halogenating agent represented by the above formula (15) alsocan be prepared by carrying out a halogen exchange reaction of thefluorinating agent represented by the formula (1) of the presentinvention with an alkali metal salt of chlorine, bromine or iodine atomin the inert solvent.

[0357] The reaction can be carried out by almost the same reactioncondition as the above mentioned the halogen exchange reaction.

[0358] The invention will hereinafter be illustrated further in detailby way of examples. However, these examples do not limit the scope ofthe invention. In Example 1 the concentration of2,2-difluoro-1,3-dimethylimidazolidine (hereinafter referred to simplyas DFI) in an acetonitrile solution was measured by high performanceliquid chromatography (hereinafter referred to simply as HPLC method)after converting into a derivative by reacting with aniline. Fluorineion (hereinafter referred to simply as F—) concentration was measured byabsorptiometry using an alizarin complexing reagent.

EXAMPLE 1

[0359] Synthesis of 2,2-Difluoro-1,3-Dimethyl-Imidazolidine(DFI)

[0360] To a 500 ml four necked reaction flask, 76.4 g(0.452 mol) of2-chloro-1,3-dimethyl-imidazolinium=chloride, 105.2 g(1.810 mol) ofspray dried potassium fluoride, and 320 ml of acetonitrile were charged,and reacted in a nitrogen atmosphere at 80° C. for 17 hours. Aftercooling the reaction mixture to 25° C., inorganic salts were separatedfrom the reaction mixture to obtain 414.2 g of an acetonitrile solutionof DFI(MW 136.15). DFI concentration in the solution was 11.4 wt %. Theyield was 77%.

[0361] The reaction mixture was vacuum distilled to obtain 32 g of DFIhaving purity of 97.8%. DFI had following properties.

[0362] Boiling point 47.0° C. /37 mmHg, EIMS: 136 (M⁺), 117 (M⁺—F⁺),IR(neat)cm⁻¹: 1486, 1385, 1295, 1242, 1085, 966, 711, F-analysis:Calculated 27.9%, Found 27.7%, ¹H-NMR(δ, ppm, CDCl₃, TMS basis): 2.52(s, 6H, —CH₃×2), 3.05 (s, 4H, —CH₂CH₂—), ¹³C NMR (δ, ppm, CDCl₃, −45° C.CDCl₃ basis): 31.4 (s, —CH₃×2), 47.6 (s, —CH₂CH₂—), 128.5 (t, J=230H_(z), ═CF₂), ¹⁹F NMR(δ, CDCl₃, −45° C. CFCl₃ basis): −70.9 (s, ═CF₂).IR spectrum diagram is shown in FIG. 1.

EXAMPLE 2

[0363] Synthesis of Bis-Dimethylamino-Difluoro-Methane (HereinafterReferred to Simply as TMF)

[0364] To a solution of 33.32 g (0.224 mol) oftetramethyl-chloroformamidinium=chloride in 107.82 g of acetonitrile,52.06 g (0.896 mol) of spray dried potassium fluoride and 33.66 g ofacetonitrile were added and reacted at 85° C. for 52 hours.Successively, the reaction mass was filtered to obtain an acetonitrilesolution of TMF. Properties of TMF were measured by using theacetonitrile solution. Properties are as follows.

[0365] EIMS: 138(M⁺), 119 (M—F)⁺, F-analysis: Calculated 12.4%, Found12.1%, ¹H-NMR (δ, ppm, CH₃CN solvent, CH₃CN basis, 24° C.): 2.44 (s,—CH₃), ¹³C NMR(δ, ppm, CH₃CN solvent, 24° C. DMSO-d₆ basis): 36.1 (s,—CH₃×4), 128.6 (t, ═CF₂).

EXAMPLE 3

[0366] Synthesis of bis-di-n-butylamino-difluoro-methane (HereinafterReferred to Simply as TBF)

[0367] To a solution of 74.36 g(0.2129 mol) oftetra-n-butyl-chloroformamidinium=chloride in 181.45 g of acetonitrile,50.92 g (0.8864 mol) of spray dried potassium fluoride and 7.86 g ofacetonitrile were added and reacted at 85 for 35 hours. Thereafter, thereaction mass was filtered. The filtrate was separated into two layers.The two layers were mixed and acetonitrile was distilled off underreduced pressure. The resulting residue was TBF. The residue hadfollowing properties.

[0368] EIMS: 306(M⁺), 287 (M—F)⁺, F-analysis: Calculated 12.4%, Found12.1%, ¹H-NMR (δ, ppm, No solvent dilution, CH₃CN basis, 24° C.:1.04(tj=˜8 Hz, CH₂CH₃), 1.41 (m,j=˜8 Hz, CH₂CH₂CH₃), 1.59(quint, j=˜8Hz, CH₂CH₂CH₂), 2.92 (t,j=˜8 Hz, NCH₂CH₂),, ¹³C NMR(δ, ppm, No solventdilution, 24° C., DMSO-d₆ basis): 12.8(CH₂CH₃), 19.6(CH₂CH₂CH₃),30.2(CH₂CH₂CH₂), 46.3(NCH₂CH₂), 128.2 (t,j=248 Hz, CF₂).

EXAMPLE 4

[0369] Synthesis of 2,2-Sifluoro-1,3-di-n-butyl-imidazolidine(Hereinafter Referred to Simply as DFB)

[0370] To a reaction vessel, 51.7 g (0.184 mol) of2-chloro-1,3-di-n-butyl-imidazolinium=chloride having purity of 90%, 174g of acetonitrile and 64.3 g (1.11 mol) of spray dried potassiumfluoride were charged and reacted at 85° C. for 25 hours under slightlyincreased pressure of nitrogen. After cooling, the reaction mass wasfiltered to obtain an acetonitrile solution of DFB. Properties weremeasured by using the solution.

[0371]¹H-NMR (δ, ppm, CDCl₃, TMS basis, 25° C.): 0.93 (t,j=˜8 Hz,CH₂CH₃), 1.40(m,j=˜8 Hz, CH₂CH₂CH₃), 1.56(quint, j=˜8 Hz, CH₂CH₂CH₃),2.95 (t,j=˜8 Hz, NCH₂CH₂), 3.24 (s, NCH₂CH₂N), ¹³C NMR(δ, ppm, CDCl₃,−65° C. CDCl₃ basis): 13.4(s, CH₂CH₃) 19.4(s, CH₂CH₂CH₃), 29.1(s,CH₂CH₂CH₂), 45.1 (s, NCH₂CH₂CH₂), 45.5(s, NCH₂CH₂N), 128.9 (t,j=228Hz,CF₂).

EXAMPLE 5

[0372] Synthesis of Benzoyl Fluoride

[0373] To a reaction vessel, 23.89 g (0.02 mol) of a 11.4 wt % solutionof DFI in acetonitrile which was obtained by similar procedures asExample 1, 2.44 g (0.02 mol) of benzoic acid and 8 ml of acetonitrilewere charged and reacted at 25° C. for 4 hours in a nitrogen atmosphere.After finishing the reaction, a portion of the reaction mixture wastaken out and a GC-MS measurement was carried out. As a result,formation of benzoyl fluoride (master ion, 124) was confirmed. The yieldof the reaction was 98% by GC analysis.

COMPARATIVE EXAMPLE 1

[0374] Synthesis of Benzoyl Fluoride

[0375] To a reaction vessel, 0.79 g(3.0 mol) of2-fluoro-1,3-dimethyl-imidazolinium=hexafluorophosphate obtained inaccordance with a preparation process described in WO96/04297, 0.24 g(2.0 m mol) of benzoic acid and 15 ml of acetonitrile were charged andreacted at 25° C. for 4 hours in a nitrogen atmosphere. After finishingthe reaction, GC analysis was carried out on the reaction mixture. As aresult, benzoyl fluoride was formed in the yield of 77%.

EXAMPLE 6

[0376] Synthesis of Benzyl Fluoride

[0377] To a reaction vessel, 1.783 g(1.50 m mol) of a 11.4 wt % solutionof DFI in acetonitrile which was obtained by similar procedures asExample 1, 0.162 g (1.50 m mol) of benzyl alcohol and 6 ml ofacetonitrile were charged and reacted at 25° C. for 4 hours in anitrogen atmosphere. After finishing the reaction, a GC-MS measurementwas carried out on the reaction mixture. As a result, formation ofbenzyl fluoride (master ion, 110) was confirmed. The yield of thereaction was 83% by GC analysis.

COMPARATIVE EXAMPLE 2

[0378] Synthesis of Benzyl Fluoride

[0379] To a reaction vessel, 0.40 g(1.5 m mol) of2-fluoro-1,3-dimethyl-imidazolinium=hexafluorophosphate obtained inaccordance with a preparation process described in WO96/04297, 0.162 g(1.5 m mol) of benzyl alcohol and 6 ml of acetonitrile were charged andreacted at 25° C. for 4 hours in a nitrogen atmosphere. Thereafter GCanalysis was carried out on the reaction mixture. As a result, benzylfluoride was not detected.

EXAMPLE 7

[0380] Synthesis of n-octyl Fluoride

[0381] To a reaction vessel, 1.79 g(1.50 m mol) of a 11.4 wt % solutionof DFI in acetonitrile which was obtained by the same procedures asExample 1, 0.195 g (1.50 m mol) of n-octyl alcohol and 4 ml ofacetonitrile were charged and reacted at 25° C. for 4 hours in anitrogen atmosphere. After finishing the reaction, GC-MS measurement wascarried out on the reaction mixture. Formation of n-octyl fluoride(master ion, 132) was confirmed. The yield was 80%.

EXAMPLE 8

[0382] Synthesis of n-octyl Fluoride

[0383] To a reaction vessel, 4.15 g(5.29 m mol) of a 17.56 wt % solutionof TMF in acetonitrile which was prepared in Example 2, 0.275 g (2.55 mmol) of n-octyl alcohol and acetonitrile were charged and reacted at 25for 4 hours in a nitrogen atmosphere. After finishing the reaction,formation of n-octyl fluoride (master ion, 132) was confirmed by GC-MSmeasurement on the reaction mixture. The yield of the reaction was 96%by GC analysis.

EXAMPLE 9

[0384] Synthesis of n-octyl Fluoride

[0385] To a reaction vessel, 0.9 g(2.9 m mol) of TBF having purity of91% which was prepared in Example 3, 0.15 g (1.15 μm mol) of n-octylalcohol and 6 ml of acetonitrile were charged and reacted at 25° C. for4 hours in a nitrogen atmosphere. After finishing the reaction,formation of n-octyl fluoride (master ion, 132) was confirmed by GC-MSmeasurement on the reaction mixture. The yield of the reaction was 98.2%by GC analysis.

EXAMPLE 10

[0386] Synthesis of n-octyl Fluoride

[0387] To a reaction vessel, 1.61 g(0.77 m mol) of DFB having purity of13% which was prepared in Example 4, 0.12 g (0.77 m mol) of n-octylalcohol and 2 ml of acetonitrile were charged and reacted at 25° C. for1 hour in a nitrogen atmosphere. After finishing the reaction, formationof n-octyl fluoride (master ion, 132) was confirmed by GC-MS measurementon the reaction mixture. The yield of the reaction was 90% by GCanalysis.

COMPARATIVE EXAMPLE 3

[0388] Synthesis of n-octyl Fluoride

[0389] To a reaction vessel, 0.40 g(1.5 m mol) of2-fluoro-1,3-dimethyl-imidazolinium=hexafluorophosphate which wasprepared in accordance with the preparation process described inWO96/04297, 0.195 g (1.5 m mol) of n-octyl alcohol and 6 ml ofacetonitrile were charged and reacted at 25° C. for 4 hours in anitrogen atmosphere. Thereafter, GC analysis was carried out on thereaction mixture. n-Octyl fluoride was not detected.

EXAMPLE 11

[0390] Synthesis of t-amyl Fluoride

[0391] To a reaction vessel, 7.74 g(6.48 m mol) of a 11.4 wt % DFIsolution in acetonitrile which was obtained by the same procedures asExample 1, and 0.285 g (3.24 m mol) of t-amyl alcohol were charged andreacted at 25° C. for 1 hour in a nitrogen atmosphere. After finishingthe reaction, formation of t-amyl fluoride (master ion, 90) wasconfirmed by GC-MS measurement on the reaction mixture. The yield of thereaction was 62%.

EXAMPLE 12

[0392] Synthesis of 1,3-Difluorobutane

[0393] To a reaction vessel, 7.74 g(6.48 m mol) of a 11.4 wt % solutionof DFI in acetonitrile which was obtained by the same procedures asExample 1, and 0.29 g (3.24 m mol) of 1,3-butanediol were charged andreacted at 25° C. for 1 hour in a nitrogen atmosphere. After finishingthe reaction, formation of 1,3-difluorobutane (master ion, 93) wasconfirmed by GC-MS measurement on the reaction mixture. The yield of thereaction was 61%.

EXAMPLE 13

[0394] Synthesis of Difluorodiphenylmethane

[0395] To a reaction vessel, 2.43 g(17.8 m mol) of DFI obtained by thesame procedures as Example 1, 1.63 g (8.9 m mol) of benzophenone and 20ml of acetonitrile were charged and reacted at 84° C. for 28 hours in anitrogen atmosphere. After finishing the reaction, formation ofdifluorodiphenylmethane (master ion, 204, base peak 127) was confirmedby GC-MS measurement on the reaction mixture. The yield of the reactionwas 45% by GC analysis.

EXAMPLE 14

[0396] Synthesis of 1,1-Difluorohexane and 1-Fluoro-1-Cyclohexene

[0397] To a reaction vessel, 1.99 g(11.7 m mol) of DFI obtained by thesame procedures as Example 1, 0.85 g (8.6 m mol) of cyclohexanone, 8.5 gof 1,2-dimethoxyethane and 0.15 g of 25% fuming sulfuric acid werecharged and reacted at 20 to 25° C. for 96 hours in a nitrogenatmosphere. After finishing the reaction, formation of1,1-difluorohexane (master ion, 120) and 1-fluoro-1-cyclohexene (masterion, 100) was confirmed by GC-MS measurement on the reaction mixture.The yield of 1-fluoro-1-cyclohexane in the reaction was 77% by GCanalysis.

EXAMPLE 15

[0398] Synthesis of α,α-Dichloro-Difluoro-Diphenylmethane

[0399] To a reaction vessel, 12.2 g(10.2 m mol as DFI) of a DFI solutionin acetonitrile which was obtained by the same procedures as Example 1,and 1.26 g (5.04 m mol) of 4,4′-dichloro-benzophenone were charged andreacted at 84° C. for 24 hours. After finishing the reaction, formationof 4,4′-dichloro-difluorodiphenylmethane (master ion, 272) was confirmedby GC-MS measurement on the reaction mixture. The yield of4,4′-dichloro-difluorodiphenylmethane in the reaction was 90% by GCanalysis.

EXAMPLE 16

[0400] Synthesis of α,α-Difluorotoluene

[0401] To a reaction vessel, 12.43 g(17.8 m mol) of DFI obtained by thesame procedures as Example 1, 0.93 g (8.8 m mol) of benzaldehyde and 25ml of acetonitrile were charged and reacted at 80 for 8 hours in anitrogen atmosphere. After finishing the reaction, formation ofαα-difluorotoluene (master ion, 128) was confirmed by GC-MS measurementon the reaction mixture. The yield in the reaction was 80% by GCanalysis.

EXAMPLE 17

[0402] Synthesis of 4,4′-Difluorobenzophenone

[0403] To a reaction vessel, 4.08 g(30.00 m mol) of DFI obtained by thesame procedures as Example 1, 1.07 g (5.00 m mol) of4,4′-dihydroxybenzophenone and 50 ml of acetonitrile were charged andreacted at 84° C. for 2 hours in a nitrogen atmosphere. After finishingthe reaction, formation of 4,4′-difluorobenzophenone (master ion, 218,base peak 123) was confirmed by GC-MS measurement on the reactionmixture. The yield in the reaction was 20% by GC analysis.

EXAMPLE 18

[0404] Synthesis of Methallyl Fluoride

[0405] To a reaction vessel, 1.783 g(1.50 m mol) of a 11.4 wt % solutionof DFI in acetonitrile which was obtained by the same procedures asExample 1, 0.108 g (1.50 m mol) of methallyl alcohol and 6 ml ofacetonitrile were charged and reacted at 25° C. for 4 hours in anitrogen atmosphere.

[0406] After finishing the reaction, formation of methallyl fluoride(master ion, 74) was confirmed by GC-MS measurement on the reactionmixture. The yield of the reaction was 95% by GC analysis.

EXAMPLE 19

[0407] Synthesis of Cyclohexyl Fluoride

[0408] To a reaction vessel, 1.783 g(1.50 m mol) of a 11.4 wt % solutionof DFI in acetonitrile which was obtained by the same procedures asExample 1, 0.150 g (1.50 m mol) of cyclohexanol and 6 ml of acetonitrilewere charged and reacted at 25° C. for 4 hours in a nitrogen atmosphere.After finishing the reaction, formation of cyclohexyl fluoride (masterion, 102) and cyclohexane (master ion, 82) was confirmed by GC-MSmeasurement on the reaction mixture. The yield of the reaction was 10%in cyclohexyl fluoride and 90% in cyclohexane, respectively by GCanalysis.

EXAMPLE 20

[0409] Synthesis of Isopropyl Fluoride

[0410] To a reaction vessel, 1.783 g(1.50 m mol) of a 11.4 wt % solutionof DFI in acetonitrile which was obtained by the same procedures asExample 1, 0.09 g (1.50 m mol) of isopropyl alcohol and 6 ml ofacetonitrile were charged and reacted at 25° C. for 4 hours in anitrogen atmosphere. After finishing the reaction, formation ofisopropyl fluoride (master ion, 62) and propylene (master ion, 42) wasconfirmed by GC-MS measurement on the reaction mixture. The yield of thereaction was 80% in isopropyl fluoride and 20% in propylene,respectively by GC analysis.

EXAMPLE 21

[0411] Synthesis of p-Fluoronitrobenzene

[0412] To a reaction vessel, 41.6 g(40.8 m mol) of a 13.6 wt % DFIsolution in acetonitrile, 2.84 g (20.4 μm mol) of p-nitrophenol and 2.03g (20.1 m mol) of triethylamine were charged and reacted at 84° C. for15 hours in a nitrogen atmosphere. After finishing the reaction,formation of p-fluoronitrobenzene (master ion, 141) was confirmed byGC-MS measurement on the reaction mixture. The yield of the reaction was60% by GC analysis.

EXAMPLE 22

[0413] Synthesis of p-Fluoronitrobenzene

[0414] To a reaction vessel, 20. g(16.0 m mol) of a 10.7 wt % DFIsolution in acetonitrile, 1.256 g (8.10 m mol) of p-nitrothiophenol werecharged and reacted at 84° C. for 16 hours in a nitrogen atmosphere.After finishing the reaction, the reaction mass was poured into 20 ml ofsaturated aqueous sodium hydrogen carbonate solution to hydrolyze DFI,successively acidified with conc.HCl to pH 2 or less and extracted with50 ml of dichloromethane. Formation of p-fluoronitrobenzene (master ion,141) was confirmed by GC-MS measurement on the reaction mixture. Theyield of the reaction was 20% by GC analysis.

EXAMPLE 23

[0415] Synthesis of 2,4-Dinitrofluorobenzene

[0416] To a reaction vessel, 1.64 g(8. 10 m mol) of2,4-dinitrochlorobenzene, 2.21 g (16.23 m mol) of DFI, and 25 ml ofacetonitrile were charged and reacted at 84° C. for 7 hours in anitrogen atmosphere. After finishing the reaction, formation of2,4-dinitrofluorobenzene (master ion, 186, base peak 94) was confirmedby GC-MS measurement on the reaction mixture. The yield of the reactionwas 96.0% by GC analysis.

EXAMPLE 24

[0417] Synthesis of Dichlorofluoronitrobenzene

[0418] To a reaction vessel, 0.74 g(2.50 m mol) ofpentachloronitrobenzene, 1.77 g (13.00 m mol) of DFI, and 25 ml ofacetonitrile were charged and reacted at 84° C. for 2 hours in anitrogen atmosphere. After finishing the reaction, formation ofdichlorotrifluoronitrobenzene (master ion, 245, master ion +2 247,master ion +4 249, base peak 245) was confirmed by GC-MS measurement onthe reaction mixture, and the yield was 28.0% by GC analysis. Formationof trichloro-difluoronitrobenzene (master ion 261, master ion +2 263,master ion +4 265, base peak 205) was also confirmed and the yield was11.3%. Formation of tetrachlorofluoronitrobenzene (master ion 277,master ion+2 279, master ion+4 281, master ion+6 283, base peak 221) wasfurther confirmed and the yield was 9.0%.

EXAMPLE 25

[0419] Synthesis of Benzoyl Fluoride

[0420] To a reaction vessel, 1.41 g(10.03 m mol) of benzoyl chloride,1.63 g (11.97 m mol) of DFI, and 25 ml of acetonitrile were charged andreacted at 84° C. for 2 hours in a nitrogen atmosphere. After finishingthe reaction, formation of benzoyl fluoride (master ion, 124, base peak124) was confirmed by GC-MS measurement on the reaction mixture. Theyield of the reaction was 71.0% by GC analysis.

EXAMPLE 26

[0421] Synthesis of 2-Fluoro-1,3-Dimethylimidazolinium Chloride(DMFC)

[0422] To a 200 ml four necked reaction flask, 30.42 g (0.1799 mol) of2-chloro-1,3-dimethylimidazolinium chloride(DMC), 15.11 g (0.3598 mol)of sodium fluoride and 104.9 g of acetonitrile were charged and reactedat 85° C. for 8 hours in a nitrogen atmosphere. After cooling thereaction mixture to 25° C., inorganic salt was separated from thereaction mixture to obtain 116.09 g of an acetonitrile solution of DMFC(MW. 152.60). Concentration of DMFC in the solution was 21.01 wt %, andthe yield was 89%.

[0423] Physical properties were as follows.

[0424] FABMS; 117[(M—Cl)⁺], 269 [(2×M—Cl)⁺], F-analysis: calculated 2.6wt %, found 2.7 wt %. Cl-analysis: calculated 4.8 wt %, found 4.9 wt %.¹H-NMR (δ, ppm, CH₃CN solvent, CH₃CN basis, 25° C.): 2.98 (s, 6H,—CH₃×2), 3.91 (s, 4H, —CH₂CH₂—). ¹³C-NMR(δ, ppm, CH₃CN solvent, DMSO-d₆base, 25° C.): 31.3 (s, —CH₃×2), 46.8 (s, —CH₂CH₂—), 157.7 (d,J=280 Hz,C—F).

EXAMPLE 27

[0425] Synthesis of n-octyl Chloride

[0426] To a reaction vessel, 0.5789 g (4.445 m mol) of n-octyl alcohol,and 3.29 g of an 21.01 wt % solution of DMFC in acetonitrile (0.691 g,4.530 m mol as DMFC) were charged and reacted at room temperature for 5hours in a nitrogen atmosphere. After finishing the reaction, GCanalysis of the reaction mixture revealed 93.1% yield of n-octylchloride. Unreacted n-octyl alcohol was 6.6%.

COMPARATIVE EXAMPLE 4

[0427] Synthesis of n-octyl Chloride

[0428] To a reaction vessel, 0.7333 g (5.631 m mol) of n-octyl alcohol,and 0.956 g (5.655 m mol) of DMC and 3.8 g of acetonitrile were chargedand reacted at room temperature for 6 hours in a nitrogen atmosphere.After finishing the reaction, GC analysis of the reaction mixturerevealed 29.3% yield of n-octyl chloride. Unreacted n-octyl alcohol was70.0%.

EXAMPLE 28

[0429] Synthesis of n-benzoyl Chloride

[0430] To a reaction vessel, 0.566 g (4.636 m mol) of benzoic acid and3.34 g of 21.01 wt % DMFC solution in acetonitrile (0.707 g, 4.636 m molas DMFC) were charged and reacted at room temperature for 3 hours in anitrogen atmosphere. After finishing the reaction, GC analysis of thereaction mixture revealed that the yield of benzoyl chloride was 91.9%and the yield of benzoyl fluoride was 8.0%.

EXAMPLE 29

[0431] Synthesis of α-Chloro-α-Fluorotoluene

[0432] To a reaction vessel, 0.9935 g (9.361 m mol) of benzaldehyde and6.81 g of 21.01 wt % DMFC solution in acetonitrile (1.431 g, 9.4 m molas DMFC) were charged and reacted at 85° C. for 17 hours in a nitrogenatmosphere. After finishing the reaction, formation ofα-chloro-α-fluorotoluene (master ion 144, base peak 109) and formationof benzal chloride (master ion 160, base peak 125) were confirmed byGC-MS measurement of the reaction mixture. The yield ofα-chloro-α-fluorotoluene was 63.6%, the yield of benzal chloride was19.7% and the unreacted benzaldehyde was 14.5% by GC analysis.

EXAMPLE 30

[0433] Synthesis of 2-Fluoro-1,3-Dimethylimidazolinium Bromide(DMFB)

[0434] To a 300 ml four necked flask, 13.78 g (0.101 mol) of2,2-difluoro-1,3-dimethylimidazolidine(DFI), 10.25 g (0.0995 mol) ofsodium bromide, and 126.5 g of acetonitrile were charged and reacted at25° C. for 4 hours in a nitrogen atmosphere. The yield of2-fluoro-1,3-dimethylimidazolinium=bromide was 99%.

[0435] Physical properties were as follows.

[0436] FABMS; 117[(M—Br)⁺], 313 [(2×M—Br)⁺], 315[isotope of (2×M—Br)+].Br-analysis: calculated 10.51 wt %, found 10.42 wt %. ¹H-NMR (δ,ppm,CH₃CN solvent, CH₃CN basis, 22° C.): 3.00 (s, 6H, —CH₃×2), 3.92(s, 4H,—CH₂CH₂—), ¹³C-NMR (δ, ppm, CH₃CN solvent, DMSO-d₆ basis, 22° C.): 31.5(s, —CH₃×2), 46.8 (s, —CH₂CH₂—), 157.6 (d,j=278 Hz, C—F).

EXAMPLE 31

[0437] Synthesis of n-octyl Bromide

[0438] To a reaction vessel, 0.247 g (1.9 m mol) of n-octyl alcohol,1.60 g of a 25.91 wt % solution of DMFB in acetonitrile (0.414 g, 2.1 mmol as DMFB) and 3.86 g of acetonitrile were charged and reacted at roomtemperature for 5 hours in a nitrogen atmosphere. After finishing thereaction, formation of n-octyl bromide (master ion 192, base peak 135)was confirmed by GC-MS measurement of the reaction mixture. The yield ofn-octyl bromide was 98.8% by GC analysis.

EXAMPLE 32

[0439] Synthesis of Benzoyl Bromide

[0440] To a reaction vessel, 0.24 g (2.0 m mol) of benzoic acid, 1.60 gof a 25.91 wt % DMFB solution in acetonitrile (0.414 g, 2.1 m mol asDMFB), and 3.86 g of acetonitrile were charged and reacted at roomtemperature for 43 hours in a nitrogen atmosphere. The results of thereaction by GC analysis were 11.0% in benzoyl bromide, 31.5% in benzoylfluoride, 26.0% in benzoic anhydride, and 16.0% in unreacted benzoicacid.

EXAMPLE 33

[0441] Synthesis of 2-Fluoro-1,3-Dimethylimidazolinium Iodide (DMFI)

[0442] To a 300 ml four necked flask, 13.56 g (0.10 mol) of2-fluoro-1,3-dimethylimidazolidine (DFI), 15.0 g (0.10 mol) of sodiumiodide and 125 g of acetonitrile were charged and reacted at 25° C. for4 hours in a nitrogen atmosphere under light shielding. The yield of2-fluoro-1,3-dimethylimidazolinium=iodide (DMFI) was 95%.

[0443] Physical properties were as follows.

[0444] FABMS; 117 [(M−1)⁺], 361 [(2×M−1)⁺]. F analysis : calculated 2.47wt %, found 2.77 wt %. I analysis: calculated 16.38 wt %, found 16.41 wt%. ¹H-NMR (δ, ppm, CH₃CN solvent, CH₃CN base, 24° C.): 3.02 (s, 6H,—CH₃×2), 3.93 (s, 4H, —CH₂CH₂—). ¹³C-NMR (δ, ppm, CH₃CN solvent, DMSO-d₆basis, 24° C.): 31.6 (s, —CH₃×2), 46.7 (s, —CH₂CH₂—), 157.6 (d,J=278 Hz,C—F).

EXAMPLE 34

[0445] Synthesis of Benzyl Iodide

[0446] To a reaction vessel, 0.216 g (2.0 m mol) of benzyl alcohol, 1.92g of a 31.73 wt % DMFI solution in acetonitrile (0.610 g, 2.5 in mol asDMFI) and 3.8 g of acetonitrile were charged and reacted at roomtemperature for 5 hours in a nitrogen atmosphere under light shielding.After finishing the reaction, formation of benzyl iodide (master ion218, base peak 92) was confirmed by GC-MS measurement of the reactionmixture. The yield of benzyl iodide was 92.2% by GC analysis.

EXAMPLE 35

[0447] Synthesis of Benzoyl Fluoride

[0448] To a reaction vessel, 0.60 g (4.91 m mol) of benzoic acid, 4.13 gof a 31.73 wt % DMFI solution in acetonitrile (1.31 g, 5.36 m mol asDMFI) and 3.8 g of acetonitrile were charged and reacted at roomtemperature for 12 hours in a nitrogen atmosphere under light shielding.Reaction result by GC analysis were 35.7% in benzoyl fluoride, 17.2% inbenzoic anhydride and 40.6% in unreacted benzoic acid.

EXAMPLE 36

[0449] Synthesis of 2-Iodo-1,3-Dimethylimidazolinium=Iodide

[0450] To a 100 ml four necked flask, 8.45 g (0.05 mol) of2-chloro-1,3-dimethylimidazolinium=chloride, 29.98 g (0.20 mol) ofsodium iodide, and 60 ml of acetonitrile were charged and reacted at 25°C. for 55 hours in a nitrogen atmosphere under light shielding. Afterfinishing the reaction, 500 ml of dry acetone was added to a slurry likereaction mass, excess sodium iodide and unreacted2-chloro-1,3-dimethylimidazolinium=chloride were extracted into theorganic solvent layer, and the reaction mass was filtered to obtaincrude crystals of the desired product as a filter cake. The crudecrystals of 2-iodo-1,3-dimethylimidazolinium=iodide has purity of 63.58%and contained sodium chloride.

[0451] Physical properties were as follows.

[0452] I-analysis : calculated 45.84%, found 44.9%. ¹H-NMR (δ, ppm,D₂O/CD₃CN=2/1, TMS basis,): 3.19 (s, 6H, —CH₁₃×2), 3.97 (s, 4H,—CH₂CH₂—). ¹³C-NMR (δ, ppm, D₂O/CD₃CN=2/1, CD₃CN basis): 37.7 (s,—CH₃×2), 50.6(—CH₂CH₂—), 134.9 (C—I).

EXAMPLE 37

[0453] Synthesis of 2-Fluoro-1,3-Dimethylimidazolinium=Iodide

[0454] To a 100 ml four necked flask, 19.78 g (0.017 mol) of a 11.7 wt %DFI solution in acetonitrile, 2.55 g(0.017 mol) of sodium iodide, and 10ml of acetonitrile were charged and reacted at 25° C. for 3 hours in anitrogen atmosphere under light shielding.2-Fluoro-1,3-dimethylimidazolinium=iodide was thus prepared.

EXAMPLE 38

[0455] Synthesis of Benzyl Iodide

[0456] To a 100 ml four necked flask, 8.45 g (0.05 mol) of2-chloro-1,3-dimethylimidazolinium=chloride, 29.98 g (0.20 mol) ofsodium iodide and 60 ml of acetonitrile were charged and reacted at 25°C. for 55 hours in a nitrogen atmosphere under light shielding.Successively, 5.4 g (0.05 mol) of benzyl alcohol was added to thereaction mass and reacted at 60° C. for 24 hours in a nitrogenatmosphere under light shielding. After finishing the reaction,formation of benzyl iodide (master ion, 218) was confirmed by GC-MSmeasurement of the reaction mixture. The yield of the reaction was 62%.

EXAMPLE 39

[0457] Synthesis of Benzyl Iodide

[0458] To 2-fluoro-1,3-dimethylimidazolinium=iodide which was obtainedin Example 33, 1.2 g(0.01 1 mol) of benzyl alcohol was added and reactedat 25° C. for 24 hours in a nitrogen atmosphere under light shielding.After finishing the reaction, formation of benzyl iodide (master ion218) was confirmed by GC-MS measurement. The yield in the reaction was90%.

EXAMPLE 40

[0459] Synthesis of 1,3-Dimethyl-2-chloro-Imidazolinium=Iodide(DMCI)

[0460] To a 100 ml four necked reaction flask, 16.90 g (0.10 mol) of2-chloro-1,3-dimethylimidazolinium=chloride, 14.99 g (0.100 mol) ofsodium iodide and 60 g of acetonitrile were charged and reacted at roomtemperature for 40 hours in a nitrogen atmosphere under light shielding.The inorganic salt was filtered off from the reaction mixture to obtain82.6 g a DMCI/actonitrile solution having a concentration of 27.3%. Theyield of DMCI was 86.6%.

[0461] The concentration of DMCI was determined by reacting DMCI withaniline and measuring the resultant derivative with high performanceliquid chromatography. Concentration of chlorine ion and iodine ion wasmeasured with a silver nitrate titration method. The scanning range ofGC-MS was 500≧M/Z≧50.

[0462] Properties were as follows.

[0463] Iodine content of the above solution : calculated 13.3%, found13.1%. Chlorine content of the above solution: calculated 3.7%, found3.8%. ¹H-NMR (δ, ppm, CH₃CN solvent, CH₃CN basis, 21° C.): 3.12 (s, 6H,—CH₃×2), 4.00 (s, 4H, —CH₂CH₂—). ¹³C-NMR (δ, ppm, CH₃CN solvent, DMSO-d₆base, 21): 34.5 (s, —CH₃×2), 49.9 (s, —CH₂CH₂—), 155.9 (s, ═C—Cl).FAB-MS (matrix: m-nitrobenzyl alcohol): [(DMCI-I)+], 393[(2× DMCI-I)+].

EXAMPLE 41

[0464] Synthesis of Benzyl Iodide

[0465] To a reaction vessel, 1.08 g (9.98 m mol) of benzyl alcohol, and11.43 g of 27.3 wt % DMCI solution in acetonitrile (3.12 g, 11.98 m molas DMCI) were charged and reacted at 60° C. for 40 hours in a nitrogenatmosphere under light shielding. After finishing the reaction,formation of benzyl iodide (master ion 218, base peak 92) was confirmedby GC-MS measurement of the reaction mixture. The yield of benzyl iodidewas 86.5% by GC analysis.

EXAMPLE 42

[0466] Synthesis of Benzoyl Chloride

[0467] To a reaction vessel, 1.22 g (9.99 m mol) of benzoic acid, 11.43g of a 27.3 wt % DMCI solution in acetonitrile (3.12 g, 11.98 m mol asDMCI), and 20.0 g of acetonitrile were charged and reacted at 60° C. for24 hours in a nitrogen atmosphere under light shielding. After finishingthe reaction, formation of benzoyl chloride (master ion 140, base peak105) was confirmed by GC-MS measurement and GC analysis of the reactionmixture.

[0468] Benzoic anhydride (base peak 105) was formed as a by-product. Theyield in the reaction is individual 92.5% in benzoyl chloride and 5.5%in benzoic anhydride.

EXAMPLE 43

[0469] Synthesis of 1,3-Dimethyl-2-Chloro-Imidazolinium=Bromide(DMCB)

[0470] To a 500 ml four necked reaction flask, 50.00 g (0.296 mol) of2-chloro-1,3-dimethylimidazolinium=chloride, 30.86 g (0.300 mol) ofsodium bromide and 240 ml of acetonitrile were charged and reacted at80° C. for 30 hours in a nitrogen atmosphere. The reaction mixture washot filtered at 70° C. or more to remove inorganic salt. The solvent waseliminated from the filtrate to obtain a solid. Recrystallization wascarried out by using 0.7 ml of acetonitrile for 1 g of the precipitatedsolid. DMCB thus obtained was 37.5 g as white crystal. The yield was59.34%.

[0471] Physical properties were as follows.

[0472] Bromine analysis: calculated 37.4%, found 37.7%. Chlorineanalysis: calculated 16.6%, found 16.4%. ¹H-NMR (δ, ppm, CD₃CN solvent,TMS basis, 21° C.): 3.15 (s, 6H, —CH₃×2), 4.00 (s, 4H, —CH₂CH₂—).¹³C-NMR (δ, ppm, CD₃CN solvent, CD₃CN-d₆ basis, 21): 35.2 (s, —CH₃×2),50.8 (s, —CH₂CH₂—), 156.3 (s, ═C—Cl). FABMS (matrix :m-nitrobenzylalcohol): 133[(DMCB-Br)+], 347[(2× DMCB-Br)+peak of isotope].

EXAMPLE 44

[0473] Synthesis of n-octyl Bromide

[0474] To a reaction vessel, 1.30 g (9.98 m mol) of n-octyl alcohol,2.14 g (10.02 m mol) of DMCB and 50 ml of acetonitrile were charged andreacted at 84° C. for 33 hours. After finishing the reaction, formationof n-octyl bromide (base peak 55, coincidence with a standard chart) wasconfirmed by GC-MS measurement of the reaction mixture. The yield in thereaction was 96% by GC analysis.

EXAMPLE 45

[0475] Synthesis of Benzyl Bromide

[0476] To a reaction vessel, 1.08 g (9.99 m mol) of benzyl alcohol, 2.14g (10.02 m mol) of DMCB and 50 ml of acetonitrile were charged andreacted at 84° C. for 24 hours in a nitrogen atmosphere. After finishingthe reaction, formation of benzyl bromide (master ion 170, base peak 91)was confirmed by GC-MS measurement of the reaction mixture. The yield inthe reaction was 85% by GC analysis.

EXAMPLE 46

[0477] Synthesis of Benzoyl Chloride

[0478] To a reaction vessel, 1.22 g (9.99 m mol) of benzoic acid, 2.14 g(10.02 m mol) of DMCB and 50 ml of acetonitrile were charged and reactedat 84° C. for 24 hours. After finishing the reaction, formation ofbenzoyl chloride (master ion 140, base peak 105) and benzoic anhydride(master peak 105) was confirmed by GC-MS measurement of the reactionmixture and by comparison of retention time with a reference material ofGC. The yield in the reaction was 66% and 12%, respectively.

EXAMPLE 47

[0479] Synthesis of 3,3′-Difluoro-2-Methylpropene

[0480] To a 300 ml autoclave, 1.70 g (24.3 μm mol) of methacrolein, 55 gof acetonitrile, 6.61 g(48.6 m mol) of DFI and 10 g (99 m mol) oftriethylamine were charged, closed up tightly after substituting thereaction system with nitrogen, and reacted at 100° C. for 5 hours. Theinternal pressure was increased up to 1.96×105 Pa in the course of thereaction. After cooling, a small amount of water was added to thereaction mass and GC and GC-MS measurements were successively carriedout. As a result, formation of 3,3-difluoro-2-methylpropene (master ion91) in the yield of 90% and 10% of unreacted methacrolein (master ion70) were confirmed.

EXAMPLE 48

[0481] Synthesis of 3,3′-Difluoro-Propene

[0482] To a 300 ml autoclave, 1.40 g (25 m mol) of acrolein, 55 g ofacetonitrile and 6.61 g (48.6 m mol) of DFI, and 10 g (99 m mol) werecharged, closed up tightly after substituting the reaction system withnitrogen, and reacted at 100° C. for 5 hours. The internal pressure wasincreased up to 1.96×105 Pa in the course of the reaction. Aftercooling, a small amount of water was added to the reaction mass andsuccessively GC and GC-MS measurements were carried out. As a result,formation of 3,3-difluoro-propene (master ion 78) in the yield of 88%and 12% of unreacted methacrolein (master ion 56) were confirmed.

EXAMPLE 49

[0483] Sythesis of 3,3′-Difluoro-Propene

[0484] To a reaction vessel, 5 g (4.40 m mol) of a 11 wt % DFI solutionin acetonitrile, and 0.255 g (4.40 m mol) of allyl alcohol were chargedand reacted at 25° C. for 4 hours in a nitrogen atmosphere. Afterfinishing the reaction, formation of 3-fluoropropene (master ion 60) wasconfirmed by GC-MS measurement of the reaction mixture. The yield in thereaction was 98% by GC measurement.

EXAMPLE 50

[0485] Synthesis of 2-Fluoroethylmethacrylate

[0486] To a reaction vessel, 8 g (6.48 m mol) of a 9.25% DFI solution inacetonitrile, and 0.842 g (6.48 m mol) of 2-hydroxyethylmethacrylatewere charged and reacted at 25° C. for 2 hours. After finishing thereaction, formation of 2-fluoroethylmethacrylate (master ion 132) wasconfirmed by GC-MS measurement of the reaction mixture. The yield in thereaction was 94% by GC analysis.

What is claimed is:
 1. A fluorinating agent represented by the formula(1):

wherein R¹ to R⁴ is a substituted or unsubstituted, saturated orunsaturated alkyl group, saturated or unsaturated aryl group, and arethe same or different; R¹and R² or R³ and R⁴ are individual groups orare bonded to form a ring including a nitrogen atom; or R¹and R³ areindividual groups or are bonded to form a ring including a nitrogenatom.
 2. A fluorinating agent according to claim 1 wherein thefluorinating agent represented by the formula (1) is represented by theformula (2):

wherein a is an integer of 2 or 3, R⁵ and R⁶ are substituted orunsubstituted, saturated or unsaturated lower alkyl groups having 1 to 6carbon atoms and are the same or different.
 3. A fluorinating agentaccording to claim 2 wherein the fluorinating agent represented by theformula (2) is 2,2-difluoro-1,3-dimethylimidazolidine represented by theformula (3):


4. A fluorinating agent according to claim 2 wherein the fluorinatingagent represented by the formula (2) is2,2-difluoro-1,3-dibutylimidazolidine represented by the formula (4):


5. A fluorinating agent according to claim 1 wherein the fluorinatingagent represented by the formula (1) is represented by the formula (5):

wherein R⁷ to R¹⁰ is a substituted or unsubstituted, saturated orunsaturated lower alkyl group having 1 to 6 carbon atoms, and are thesame or different; R⁷ and R⁸ or R⁹ and R¹⁰ are individual groups or arebonded to form a ring including a nitrogen atom; or R⁷ and R⁹ areindividual groups or are bonded to form a ring including a nitrogenatom.
 6. A fluorinating agent according to claim 5 wherein thefluorinating agent represented by the formula (5) isbis-dimethylamino-difluoromethane represented by the formula (6):


7. A fluorinating agent according to claim 5 wherein the fluorinatingagent represented by the formula (5) isbis-di-n-butylamino-difluoromethane represented by the formula (7):


8. A preparation process of a fluorine compound represented by theformula (8-1): R¹¹—F  (8-1) wherein R₁₁ is a substituted orunsubstituted, saturated or unsaturated alkyl group, comprising reactinga compound having an alcoholic hydroxyl group and represented by theformula (8): R¹¹—OH  (8) wherein R₁₁ is the same as in the formula(8-1), with the above fluorinating agent represented by the formula (1)in claim
 1. 9. A preparation process of a fluorine compound representedby the formula (9-1):

wherein Y₁ is an electrophilic substituent, b is an integer of 1 to 5, cis an integer of 1 to 5, and b+c≦6, comprising reacting a compound ofphenol or thiophenol represented by the formula (9):

wherein Q is an oxygen or a sulfur atom, and Y₁, b and c are the same asin the formula (9-1), with the fluorinating agent represented by theformula (1) in claim
 1. 10. A preparation process of a fluorine compoundrepresented by the formula (10-1): R¹²—CHF₂  (10-1) wherein R₁₂ is asubstituted or unsubstituted, saturated or unsaturated alkyl group, or asubstituted or unsubstituted aryl group, comprising reacting an aldehydecompound represented by the formula (10): R¹²—CHO  (10) wherein R₁₂ isthe same as in the formula (10-1), with the fluorinating agentrepresented by the formula (1) in claim
 1. 11. A preparation process ofa fluorine compound represented by the formula (1 1-1):

wherein R₁₃ and R₁₄ are a substituted or unsubstituted, saturated orunsaturated alkyl group or a substituted or unsubstituted aryl group andare the same or different; and R₁₃ and R₁₄ are individual groups or arebonded to form a ring, comprising reacting a ketone compound representedby the formula (11):

wherein R₁₃ and R₁₄ are the same as in the formula (11-1), with thefluorinating agent represented by the formula (1) in claim
 1. 12. Apreparation process of an acid fluoride represented by the formula(12-1): R¹⁵—COF  (12-1) wherein R₁₅ is a substituted or unsubstituted,saturated or unsaturated alkyl group or a substituted or unsubstitutedaryl group, comprising reacting a carboxyl compound represented by theformula (12): R¹⁵—COOH  (12) wherein R₁₅ is the same as in the formula(12-1), with the fluorinating agent represented by the formula (1). 13.A preparation process of a fluorine compound represented by the formula(13-1):

wherein Y₁ is an electrophilic substituent, b and d are integers of 1 to5, and b+d≦6, comprising reacting an aromatic compound represented bythe formula (13):

wherein X₁ is a halogen atom except fluorine, and Y₁, b and d are thesame as in the formula (13-1), with the fluorinating agent representedby the formula (1) in claim
 1. 14. A preparation process of a fluorinecontaining olefinic compound represented by the formula (25)

wherein R₁₅ to R₁₇ are a hydrogen atom or a lower alkyl group having 1to 3 carbon atoms and are the same or different; and Z is —(Y)n—CHF₂,—(Y)n—CH₂F or —CO—O—(Y)n—CH₂F, wherein Y is —CH₂— and n is 0 or aninteger of 1 to 5, comprises reacting a fluorinating agent representedby the formula (1) in claim 1 with an olefinic compound represented bythe formula(24)

wherein R₁₅ to R₁₇ are a hydrogen atom or a lower alkyl group having 1to 3 carbon atoms and are the same or different; and X is —(Y)n—CHO,—(Y)n CH₂OH, or —CO—O—(Y)n—CH₂OH, wherein Y is —CH₂— and n is 0 or aninteger of 1 to
 5. 15. A process according to claim 14 wherein thefluorinating agent is represented by the formula (2).
 16. A compoundrepresented by the formula (2) in claim 16:

wherein a is an integer of 2 or 3, R⁵ and R⁶ are a substituted orunsubstituted, saturated or unsaturated lower alkyl group having 1 to 6carbon atoms and are the same or different.
 17. A compound wherein theformula (2) in claim 16 is 2,2-difluoro-1,3-dimethylimidazolidinerepresented by the formula (3):


18. A compound wherein the formula (2) in claim 16 is2,2-difluoro-1,3-di-n-butylimidazolidine represented by the formula (4):


19. A compound wherein the formula (5) in claim 5 isbis-di-n-butylamino-difluoromethane represented by the formula (7):


20. A preparation process of a fluorinating agent represented by theformula (1) in claim 1 comprising carrying out a halogen exchangereaction of a compound represented by the formula (14):

wherein X₂ and X₃ are a chlorine or a bromine atom, R¹ to R⁴ aresubstituted or unsubstituted, saturated or unsaturated alkyl group,substituted or unsubstituted aryl group, and are the same or different;R¹ and R¹ or R³ and R⁴ are individual groups or are bonded to form aring including a nitrogen atom or a nitrogen atom and other hetero atoms; or R¹ and R³ can bond to form a ring including a nitrogen atom with analkali metal salt of a fluorine atom in an inert solvent.
 21. Apreparation process of a fluorinating agent of claim 20 comprisingreacting a compound represented by the formula (14) with a halfequivalent of sodium fluoride, separating by filtration, andsuccessively reacting with potassium fluoride.
 22. A halogenating agentrepresented by the formula (15):

wherein X₄ and X₅ are a halogen atom and can be the same or differentexcept that both X₄ and X₅ are not fluorine atoms, chlorine atoms orbromine atoms; R¹ to R⁴ are a substituted or unsubstituted, saturated orunsaturated alkyl group or a substituted or unsubstituted aryl group,and are the same or different; R¹ and R² or R³ and R⁴ are individualgroups or are bonded to form a ring including a nitrogen atom; or R¹andR³ are individual groups or are bonded to form a ring including anitrogen atom.
 23. A halogenating agent according to claim 22 whereinthe halogenating agent represented by the formula (15) is represented bythe formula(16):

wherein X₄ and X₅ are a halogen atom and are the same or differentexcept that both X₄ and X₅ are not fluorine atoms, chlorine atoms orbromine atoms ; a is an integer of 2 or 3, R⁵ and R⁶ are a substitutedor unsubstituted, saturated or unsaturated lower alkyl group having 1 to6 carbon atoms and are the same or different.
 24. A halogenating agentaccording to claim 23 wherein the halogenating agent represented by theformula (16) is 2-halo-1,3-dimethylimidazolinium=halide represented bythe formula (17):

wherein X₄ and X₅ are a halogen atom and are the same or differentexcept that both X₄ and X₅ are not fluorine atoms, chlorine atoms orbromine atoms.
 25. A halogenating agent according to claim 23 whereinthe halogenating agent represented by the formula (16) is2-fluoro-1,3-dimethylimidazolinium=chloride represented by the formula(18):


26. A halogenating agent according to claim 23 wherein the halogenatingagent represented by the formula (16) is2-fluoro-1,3-dimethylimidazolinium=bromide represented by the formula(19):


27. A halogenating agent according to claim 23 wherein the halogenatingagent represented by the formula (16) is2-fluoro-1,3-dimethylimidazolinium=iodide represented by the formula(20):


28. A halogenating agent according to claim 23 wherein the halogenatingagent represented by the formula (16) is2-chloro-1,3-dimethylimidazolinium=bromide represented by the formula(21):


29. A halogenating agent according to claim 23 wherein the halogenatingagent represented by the formula (16) is2-chloro-1,3-dimethylimidazolinium=iodide represented by the formula(22):


30. A halogenating agent according to claim 23 wherein the halogenatingagent represented by the formula (16) is2-iodo-1,3-dimethylimidazolinium=iodide represented by the formula (23);


31. A preparation process of a halogenating agent represented by theabove formula (15) according to claim 21 comprising carrying out ahalogen exchange reaction of a compound represented by the formula (14):

wherein X₂ and X₃ are a chlorine or bromine atom and R¹ to R⁴ are thesame as above, with an alkali metal salt of a fluorine atom, chlorineatom, bromine atom or iodine atom or a mixture thereof in an inertsolvent.
 32. A preparation process of a halogen compound represented bythe formula (8-2): R¹¹—X₅  (8-2) wherein R₁₁ is a substituted orunsubstituted, saturated or unsaturated alkyl group and X₅ is a halogenatom, comprising reacting an alcoholic hydroxyl compound represented bythe formula (8): R¹¹—OH  (8) wherein R₁₁ is the same as in the formula(8-2), with the halogenating agent in claim 22 represented by theformula (15):

wherein X₄, X₅, and R¹ to R⁴ are the same as above.
 33. A preparationprocess of an acid halogenide species represented by the formula (12-2):R¹⁵—,COX₆  (12-2) wherein R¹⁵ is a substituted or unsubstituted,saturated or unsaturated alkyl group or substituted or unsubstitutedaryl group and X₆ is a halogen atom represented by X₄ or X₅ in theformula (15), comprising reacting a carboxylic acid compound representedby the formula (12): R¹⁵—COOH  (12) wherein R¹⁵ is the same as in theformula (12-2), with a halogenating agent represented by the formula(15):

wherein X₄, X₅ and R¹ to R⁴ are the same as above.
 34. A preparationprocess of a halogenide compound represented by the formula (10-2):R¹²—CH(X₇)₂  (10-2) wherein R¹² is a substituted or unsubstituted,saturated or unsaturated alkyl group, or a substituted or unsubstitutedaryl group, and X₇ is a halogen atom represented by X₄ or X₅ in theformula (15) in claim 22 and two X₇ can be the same or different,comprising reacting an aldehyde compound represented by the formula(10): R¹²—CHO  (10) wherein R¹² is the same as in the formula (10-2),with a halogenating agent represented by the formula (15):

wherein X₄, X₅ and R¹ to R⁴ are the same as above.
 35. A preparationprocess of a halogen compound according to one of the claim 32 to 34wherein the halogenating agent is represented by the formula (17):
 36. Acompound represented by the formula (15):

wherein X₄ and X₅ are a halogen atom and can be the same or differentexcept that both X₄ and X₅ are fluorine atoms, chlorine atoms or bromineatoms; R¹ to R⁴ are a substituted or unsubstituted, saturated orunsaturated alkyl group or a substituted or unsubstituted aryl group andcan be the same or different; R¹ and R² or R³ and R⁴ can bond to form aring including a nitrogen atom or a nitrogen atom and other heteroatoms; or R¹ and R³ can bond to form a ring including a nitrogen atom ora nitrogen atom and other hetero atoms.
 37. A compound represented bythe formula (16):

wherein X₄ and X₅ are same or different halogen atom except that both X₄and X₅ are fluorine atom, chlorine atom or bromine atom, a is an integerof 2 or 3, R⁵ and R⁶ are a substituted or unsubstituted, saturated orunsaturated lower alkyl group having 1 to 6 carbon atoms and can be thesame or different.
 38. A halogenating agent according to claim 22wherein the halogenating agent is2-halo-1,3-dimethylimidazolidinium=halide represented by the formula(17):

wherein X4, X5 are the same as above.
 39. A compound,2-fluoro-1,3-dimethylimidazolidinium=chloride represented by the formula(18):


40. A compound, 2-fluoro-1,3-dimethylimidazolidinium=bromide representedby the formula (19):


41. A compound, 2-fluoro-1,3-dimethylimidazolidinium=iodide representedby the formula (20):


42. A compound, 2-chloro-1,3-dimethylimidazolidinium=bromide representedby the formula (21):


43. A compound, 2-chloro-1,3-dimethylimidazolidinium=iodide representedby the formula (22):


44. A compound, 2-iodo-1,3-dimethylimidazolidinium=iodide represented bythe formula (23):


45. A preparation process of a halogenating agent represented by theformula (15):

wherein X₄ and X₅ are halogen atoms and can be the same or differentexcept that both X₄ and X₅ are fluorine atoms, chlorine atoms or bromineatoms; R¹ to R⁴ is a substituted or unsubstituted, saturated orunsaturated alkyl group or a substituted or unsubstituted aryl group andcan be the same or different; R¹and R² or R³ and 5 R⁴ can bond to form aring including a nitrogen atom or a nitrogen atom and other heteroatoms, comprising carrying out a halogen exchange reaction of a compoundrepresented by the formula (1):

wherein R¹ to R⁴ are the same as above, with an alkali metal salt ofchlorine, bromine or iodine atom in the presence of an inert solvent.